3,5-dimethylbenzoyl chloride

Endpoint summary

Additional information

PARAMETERS

Physico-chemical Properties:

It has a molecular weight of 168.6 and at room temperature it is a colourless, clear liquid, with a freezing temperature of 4 °C and a boiling temperature of 239 °C. Its relative density is 1.138 at 20 °C and vapour pressure is 5.2 Pa at 25 °C. The surface tension of DMBC is 64.6 mN/m 21 °C. The substance is unstable in water, being immediately hydrolysed to the corresponding acid. The water solubility of the hydrolysis product (dimethylbenzoic acid) was 79 mg/L at 20 °C and the test substance was found to be miscible with fat in all proportions at 37 °C. The calculated partition coefficient was log Pow 2.85 (approximately).

 

Toxicity

Acute Oral Toxicity:

The LD50 for males was determined to be >5000 mg/kg, and 3162 mg/kg (with 95 % confidence limits of 2000 to 5000 mg/kg bodyweight) for females. The test range was 500, 2000, and 5000 mg/kg bodyweight. There were mortalities at the high dose level (1/6 males and 6/6 females) and clinical signs included passivity, ataxia, tremors, hyperrefiexia, convulsions and twitching of the extremities in the 5000 mg/kg dose level. Other clinical signs in the 2000 and 5000 mg/kg groups included increased salivation, prostration, scant or no faeces, red-stained drop-sheet and red-stained fur surrounding muzzle and/or eyes. The bodyweights for male rats in the 5000 mg/kg group were approximately 30 % less than historical control data. There were no macroscopically visible changes following termination of the surviving test animals. For animals which died during the course of the study, necropsy revealed primarily gastro-intestinal abnormalities such as reddened, black or mucous contents; black material adhered to the mucosa.

 

Acute Dermal Toxicity:

At a limit dose of 200 mg/kg there were no mortalities. The test substance produced some dermal reactions including erythema and some sores on the perimeter of the application site. All animals were free of systemic toxicity signs. Macroscopic examination of the animals showed no abnormalities.

 

Skin Irritation:

A single occlusive application of DMBC induced corrosive skin reactions including medium erythema and slight to medium oedema followed by ulcer formation. This ulcerated region gradually changed to scar. These reactions were not fully reversible within 19 days although the skin did show signs of healing.

 

Eye Irritation:

This test was not conducted on humane grounds. The test substance is expected to be corrosive to the eye.

 

28 Day Sub-acute Toxicity Study:

Groups of five male and five female rats received 15, 150 or 1000 mg/kg/day in corn oil via oral gavage. There were no mortalities in any group.

In the high dosage group, clinical signs included increased salivation after dosing and red/brown staining of the fur in most rats and red/brown staining of the urogenital region in females. In the 150 mg/kg/day group, increased salivation was also seen in some rats. The alkaline phosphatase (AP) concentration for males and females and the glutamic pyruvate transaminase (GPT) and glutamic oxoacetic transaminase (GOT) concentrations for females were elevated at 1000 mg/kg/day as well as minor changes in cholesterol and glucose levels. For female rats in the other two groups, elevated AP and GPT levels were also evident. Following termination, increased liver and kidney weights were recorded for the 1000 mg/kg/day group. Minimal centilobular hepatocyte enlargement in the liver was evident amongst males treated at 1000 mg/kg/day. Renal changes consisting of dilated cortical tubules with basophilic flattened epithelium, associated with casts in the lumen of the dilated tubules, were seen in both sexes treated at 1000 mg/kg/day. 150 mg/kg/day was determined to be the no observed toxic effect level in the rat.

 

Mutagenicity: Metabolism

No toxicity or mutagenic activity was seen in the Ames test, either in the absence or presence of S-9 mix. In the in vitro cytogenetics assay, DMBC was not clastogenic in the absence of S-9 mix.

 

ASSESSMENT

The moderate water solubility and high fat solubility coupled with a reasonably high estimated log Pow value suggest that DMBC is bioavailable and may bioaccumulate. DMBC is not classified on the basis of the acute oral and acute dermal toxicity studies. Animals did not exhibit any signs of systemic toxicity during the acute dermal study which implies that there is minimal to no absorption of the test substance through the skin.

 

The 28 day sub-acute toxicity study indicates that absorption, distribution, metabolism and excretion of the test substance or its hydrolysis product take place. This is manifested by changes in enzyme levels, elevated liver and kidney weights, changes in liver morphology of male rats and in the kidney morphology of male and female rats. These findings suggest that the liver and/or the kidney are the target organs for toxicity with DMBC.

CONCLUSION

The 28 day oral toxicity study provides evidence that the test substance is absorbed via this route. It also demonstrates that the test material may be distributed systemically and that metabolism occurs in the liver. Various changes in the kidneys suggest that DMBC and/or its metabolites could be excreted renally. There was no evidence of bioaccumulation or dermal absorption found.