Acetic acid, 2-[(5-chloro-8-quinolinyl)oxy]-

Endpoint summary

Description of key information

The NOAEL for repeated dose oral toxicity in rats was the highest dose tested, 2100 ppm, which corresponded to time-weighted average concentrations of 116.0 and 127.0 mg/kg bw/day in males and females, respectively. On this basis, low toxicity is also predicted for the inhalation and dermal routes of exposure.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

116 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

The 90-day repeated oral toxicity study in the rat (Sura et al, 2014) is assigned Klimisch score = 1 as it is a modern study compliant with current test guidelines and GLP. The remaining studies were non-guideline non-GLP preliminary investigations carried out with the purpose of identifying and resolving palatability issues in addition to toxicological screening and dose range selection.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

90-Day Repeat Oral Toxicity:

A 90-day repeated dose oral toxicity study (Sura et al, 2014) was conducted according to OECD test guideline 408 to evaluate the potential toxicity of cloquintocet acid in rats following dietary administration for at least 90 days. Recovery groups of the control and high concentration of cloquintocet acid were given untreated diets for an additional 28-days to evaluate the reversibility or persistence of any potential effects induced after 90 days of dietary exposure. There were no treatment-related effects in clinical signs, functional tests, ophthalmic examinations, prothrombin time, or serum thyroid hormone parameters. There were no treatment related, gross or histopathologic observations. Treatment-related decreases in body weights, body weight gains and feed consumption were attributed to decreased palatability. Treatment-related changes in platelet counts, blood urea nitrogen, urine volumes and spleen weights at the highest tested concentration were interpreted to be non-adverse. Under the conditions of this study, the NOAEL was the highest tested concentration of 2100 ppm cloquintocet acid that corresponded to time-weighted average concentrations of 116.0 or 127.0 mg/kg bw/day in males and females, respectively.

14 -Day Dietary Toxicity Screening and Palatability Study:

A 14 -day dietary toxicity screening and palatability study (Sura and Andrus, 2014a) was conducted to evaluate the potential toxicity and palatability of cloquintocet acid in F344/DuCrl rats following dietary administration for 14 days. There were no treatment-related effects or clinical signs. Treatment-related decreases in body weights/body weight gain, and feed consumption were attributed to reduced palatability of the feed. There were no treatment-related organ weight effects, gross or histopathologic observations in any of the treated groups. Based on the treatment-related effects on body weight and feed consumption at higher concentrations, the NOEL for F344/DuCrl rats of either sex was 500 ppm, corresponding to 40.3 mg/kg/day for males and 42.6 mg/kg/day for females.

 

14 -Day Dietary Palatability Study:

A 14 -day palatability study was conducted to evaluate the palatability of cloquintocet acid in Crl:Wistar Han rats. There were no treatment-related clinical observations in any dose group. Treatment-related decreases in feed consumption, body weight, and body weight gain were observed for cloquintocet acid. Based on the findings of the study it was concluded that future dietary administration studies may benefit from initiating test diet administration at a lower initial concentration such as 700 ppm and increasing to a target high dose concentration such as 2100 ppm.

 

7 -Day Dietary Palatability Study:

A study was conducted to determine if a ‘ramp-up’ study design could alleviate the previously identified palatability issues of cloquintocet acid. A treatment-related decrease in feed consumption was evident on the day following cloquintocet acid initiation and to a lesser extent following the concentration increase on test day 4. Under the conditions of the study, cloquintocet acid at dose levels of 700 and 2100 ppm may be considered for subsequent studies.

Justification for classification or non-classification

Cloquintocet acid was shown to be of relatively low toxicity following repeat oral administration; the results of the studies available for cloquintocet acid do not indicate any severe toxicity and do not show any adverse effects at dose the highest tested doses. Low toxicity is also predicted for the inhalation and dermal exposure routes. Cloquintocet acid is therefore not classified for repeated dose toxicity according to CLP Regulation No 1272/2008.