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Toxicity Effects

CAS Registry Number: 106-43-4

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 2.

Names 1

  • 4-Chlorotoluene
  • Benzene, 1-Chloro-4-Methyl-
  • p-Chlorotoluene

Human Toxicity Excerpts

  • None found

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Non-Human Toxicity Excerpts

  • Early life stage toxicity experiments were carried out for both chlorobenzene and aniline derivatives under semistatic conditions using zebra fish (Brachydanio rerio). The parameters studied included survival, embryo- hatchability and growth. From these effect parameters and the n-octanol/water partition coefficient (Poct) high quality quantitative structure-activity relationships could be derived. The aniline derivatives appeared to have a higher toxicity than the chlorobenzenes, which have a nonspecific (narcotic) mode of toxic action. For the narcotizing chemicals long-term 28-day early life stage toxicity could be accurately predicted on the basis of short-term (7-day) experiments. For the anilines, which are assumed to exert their toxic effects after metabolic activation, the predictions for long-term toxicity on the basis of short-term experiments were found to be inaccurate. For these chemicals it seems necessary either to include detailed microscopic observations for sublethal effects or to prolong the exposure period for the free-feeding larval stages. Differences in sensitivity between B. rerio (this study) and fathead minnow, Pimephales promelas (data reported in literature) were found to be small. A quantitative structure activity relationship for early life stage-toxicity for 30 narcotizing chemicals for the two species was derived. Available data on the acute toxicity of guppy Poecilia reticulata show that for chemicals with a nonspecific mode of toxic action the mean 'acute/chronic' toxicity ratio is approximately 15.[van Leeuwen CJ et al; Aquatic Toxicol 16: 321-34 (1990)] **PEER REVIEWED**
  • LC50-experiments were conducted using guppies subjected to 72 industrial pollutants. Correlation of the LC50 with several expressions of the hydrophobicity of these chemicals was studied. Calculated log Poct(partition coefficient)-values satisfied more than HPLC (high performance liquid chromatography) retention indices, solubility data or molecular connectivity indices. One quantitative structure-activity relationship, with log Poct as the only variable, gave good estimations of the toxicity of most tested compounds with log Poct, < 6. No LC50 could be determined for solutions of compounds with log Poct > 6.[Konemann H; Toxicol 19 (3): 209-22 (1981)] **PEER REVIEWED**
  • P-CHLOROTOLUENE FOUND NOT TO BE MUTAGENIC IN AMES SALMONELLA/MICROSOME ASSAY.[SIMMON ET AL; DEV TOXICOL ENVIRON SCI 2: 249-58 (1977)] **PEER REVIEWED**
  • Quantitative structure-activity relationships were calculated between hydrophobicity of a group of organic chemicals with anaesthetic potency and toxicity (immobilization, mortality and inhibition of reproduction) to Daphnia magna. Differences in slopes of the high quality quantitative structure activity relationship might have been explained in terms of possible different sites of action for the 3 criteria of effect. The combined effects of mixtures of 5-50 chemicals on immobilization and mortality did not deviate from additivity, while the effect on reproduction deviated from it.[Hermens J et al; Aquat Toxicol (AMST) 5 (2): 143-54 (1984)] **PEER REVIEWED**
  • p-Chlorotoluene was administered by corn oil gavage for 14 and 90 days to male and female Sprague-Dawley-derived rats at dosages of 200, 600, and 1800 mg/kg per day and 50, 200, and 800 mg/kg per day, respectively. In the 14-day study, 8 of 10 animals of each sex in the high-dose group died due to treatment. Other treatment-related signs for these animals included an adverse effect upon body weight and clinical signs of salivation, tremors, and prostration. In the 200 and 600 mg/kg per day groups there were no apparent treatment-related effects. In the 90-day study, 4 of 10 males and 2 of 10 females in the high-dose group died due to treatment. Other signs for this treatment group included an adverse effect upon body weight and clinical signs of languid behavior, prostration, tremors, sensitivity to touch, epistaxis, and respiratory distress. Increases in alkaline phosphatase and creatinine (males only), and increases in adrenal (absolute and relative, females), kidney (relative, both sexes), and liver (relative, both sexes) weights were also noted. Histopathologic findings of centrilobular hepatocellular hypertrophy, adrenal cortical hyperplasia, and exacerbation of chronic progressive nephropathy confirmed the clinical laboratory and organ weight results as being treatment related for the animals receiving 800 mg/kg per day for 90 days. Animals receiving 50 or 200 mg/kg per day (90 days) did not exhibit treatment-related findings.[Terrill JB et al; J Am Coll Toxicol 9 (5): 487-96 (1990)] **PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • None found

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Absorption, Distribution And Excretion

  • None found

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Metabolism/Metabolites

  • P-CHLOROTOLUENE GIVES P-CHLOROBENZOIC ACID IN RABBIT. /FROM TABLE/[Goodwin, B.L. Handbook of Intermediary Metabolism of Aromatic Compounds. New York: Wiley, 1976., p. C-43] **PEER REVIEWED**
  • Two products were isolated from a study of the metabolism of p-chlorotoluene by Pseudomonas putida: (+) cis-4-chloro-2,3-dihydroxy-1-methylcyclohex-4,6-diene and 4-chloro-2,3-dihydroxy-1-methylbenzene. The enzymatic dehydrogenation of the former compound to the latter was demonstrated.[Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. V5 823 (1979)] **PEER REVIEWED**

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Tsca Test Submissions

  • Acute dermal toxicity was evaluated in 2 male and 2 female New Zealand white rabbits exposed to a single occluded dose of undiluted parachlorotoluene to abraded and intact skin. There were no mortalities and an LD50 value was not reported. Clinical and necropsy observations revealed nothing remarkable except for diarrhea in 1 male.[Springborn Institute for Bioresearch Inc.; Dermal Toxicity (LD50) in Rabbits with Cover Letter Dated 062587, (1980), EPA Document No. 86870000415, Fiche No. OTS0513163] **UNREVIEWED**
  • Acute oral toxicity was evaluated in groups of 2 adult male albino Sprague-Dawley rats administered para-chlorotoluene by gavage as either a 1.0 or 10% volume/volume solution in corn oil or in undiluted form at dosage levels of 10, 31.6, 100, 316, 1000 or 3160 ul/kg. Mortality was observed in both rats in the 3160 ul/kg dose group (100% solution) and the LD50 was estimated to be 1780 ul/kg. Clinical observations included depression, lacrimation, labored respiration, ataxia, tremors, depressed righting and placement reflexes and prostration. Gross necropsy revealed congestion of the lungs, kidneys and adrenals and inflammation of the gastrointestinal tract in the decedents. Sacrificed animals did not display this inflammation.[Hazelton Labs Inc.; Acute Oral Dose Range-Rats with Cover Letter Dated 062587, (1964), EPA Document No. 86870000413, Fiche No. OTS0513161] **UNREVIEWED**
  • Acute oral toxicity was evaluated in groups of 5 male and 5 female fasted Sprague-Dawley rats administered 4-chlorotoluene by gavage at a level of 1.7, 2.3, 3.3 or 4.6 g/kg. Mortality was observed in 2 males in the 1.7 g/kg group, 3 males and 4 females in the 2.3 g/kg group, and in all 5 males and females in the 3.3 and 4.6 g/kg groups. The LD50 was determined to be 2.1 g/kg (1.8 - 2.4 g/kg). Clinical observations included a decrease in motor activity, tremors, cyanosis, piloerection, excess salivation, chromodacryorrhea, increase in respiratory rate, decrease in respiratory rate and lacrimation. Gross necropsy revealed bright red or red and mottled lungs, stomach and intestinal irritation and cream colored, white or dark fluid in the stomach and intestine, red stained fur around the nose, "blanched" stomachs and fluid filled stomachs.[Springborn Institute for Bioresearch, Inc.; Acute Oral Toxicity (LD50) in Rats with Cover Letter Dated 062587, (1980), EPA Document No. 86870000414, Fiche No. OTS0513162] **UNREVIEWED**
  • p-Chlorotoluene (CAS # 106-43-4) was evaluated for chromosomal effects. A single intraperitoneal injection of 1000 mg/kg body weight was administered to male and female mice. Animals were sacrificed and femoral marrow was prepared at 16-hours (5 M, 5 F); 24-hours (5 M, 5 F); and 48-hours (5 M, 5 F) after administration. Signs of toxicity included apathy, roughened fur, staggering gait, spasm, twitching, shivering, and difficulty in breathing. Two animals died during treatment. Gross necropsy revealed slightly inflated lungs and spotted livers. The ratio between polychromatic and normochromatic erythrocytes and clastogenic effect was not altered.[MILES INC; Micronucleus Test On The Mouse (Final Report) With Cover Letter Dated 04/20/92; 03/31/92; EPA Doc No. 86-920000901; Fiche No. OTS0535638] **UNREVIEWED**

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Footnotes

1 Source: the NTP's CEBS database.

2 Source: the National Library of Medicine's Hazardous Substance Database, 02/28/2017.

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