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Administrative data

Description of key information

Irvine, 1981, was selected as the key information for this end point. The study was conducted in a similar manner to the OECD 408 guideline. The study was only allocated a reliability score of 2 according to the criteria of Klimisch et al, 1997, because of deviations which affect the reliability of the study result, however in view of the findings of the study and the methodology used the study was considered to be of adequate reliability to fulfil the regulatory requirement.
The study was performed as part of a 3 generation reproduction/developmental toxicity study and was performed as a feeding study on the rat for a period of 13 weeks prior to two mating periods of 8 weeks each for a total dosing period of 29 weeks. Concentrations in feed were set to give three test groups of 1, 3 and 10mg/kg bw/day with 50 animals (25 male/25 female) in each test group.
Based upon the observations reported for parental animals (F0 generation) the NOAEL for repeat dose toxicity was set at 3mg/kg bw/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
3 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

Although the key study (Irvine) contained significant deviations from the recommended OECD guideline, the methodology and reported results were of sufficient reliability to fulfil the regulatory requirement and form the basis for the consideration of classification.

In the key study, no effects attributable to the administration of Dinoseb were observed in the evaluation of parental survival, necropsy findings, fertility, fecundity or in the various reproductive indices examined. The NOAEL value of 3 mg/kg bw/day (the middle tested dose) was based upon a statistically significant reduction in body weight gain of animals in the highest dose group (10 mg/kg bw/day) together with the appearance of a yellowish tinge in the fur of animals of the same group.

In addition to the key study, a supporting study is also available. Spencer et al, 1948, was conducted using a novel methodology, and performed on the rat. The results reported support the key study and provide a NOAEL from 2.7 -10mg/kg bw/day.

Male rats maintained for six months on diets containing 0.01% 2-sec-butyl-4,6-dinitrophenol showed no appreciable ill effects as determined by frequent gross observations, growth curves, periodic blood counts, analyses for blood urea-N, organ weights and histopathological examinations.

Effects that may be attributable to the action of dinitrophenols as metabolic stimulants, was observed in rats that received diets containing greater quantities of these materials. Thus, depression of body weights, chiefly at the expense of body fat, was the characteristic finding rather than appreciable organic injury. No cataracts were produced in any of the rats receiving the dinitrophenols nor were there any changes in the bone marrow or blood picture.

In the case of each of the dinitrophenols investigated, it is evident there is little summation of toxic effects upon prolonged ingestion, as judged by a comparison of the quantity that caused death after a single oral dose with the quantity that that produced no appreciable ill effects when administered in the diet after a period of six months.

Although there were reductions in body weight gain recorded in both studies, this alone is insufficient justification for classification. 

Justification for classification or non-classification

The results from the two repeated dose oral toxicity studies showed that there were no significant effects from Dinoseb ingestion that would indicate a requirement for classification. Although there were reductions in body weight gain recorded in both studies , this alone is insufficient justification for classification.