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Key value for chemical safety assessment

Effects on fertility

Additional information

Introduction: The study was desgined to investigate the systemic toxicity and potential adverse effects on reproduction (including offspring development) of the test item and complies with the recommendations of the OECD Guidelines for Testing of Chemicals No. 421 "Reproduction/Developmental Toxicity Screening Test" (adopted 27 July 1995).

Methods: The test item was administered by gavage to three groups each of ten male and ten female Wistar Han TM: WIST strain rats, for up to fifty four days, at dose levels of 100, 300 and 1000 mg/kg/day. A control group of ten males and ten females were dose with vehicle alone. (Arachis oil).

Clinical signs, body weight development, food and water consumption were monitored during the study.

Pairing of animals within each dose group was undertaken on a one male: one female basis on Day 15 of the study, to produce litters. During the lactation phase, daily clinical observations werte undertaken on all live offspring, together with litter size, offspring weights and assesment of developmental landmarks.

Males were terminated on Day 43, followed by termination of females and offspring on Day 5 post partum. All animals were subjected to a gross necropsy examination and preliminary histopathological evaluation was undertaken.

Results:

Mortality: There were no unscheduled deaths during the study.

Clinical Observations: There were no clinical signs of toxicity detected.

Body Weight: No adverse effects on body weight development were detected for all treated animals or recovery animals during the treatment free period when compared to controls.

Food Consumption:No adverse effects on food intake or food efficiency were detected.

Water Consumption: No intergroup differences were detected.

Reproductive Performance:

Mating:

There were no toxicologically significant effects on mating or conception rates for animals of either sex treated with 100, 300 or 1000 mg/kg/day.

One females treated with 1000 mg/kg/day and one females treated with 100 mg/kg/day failed to achieve pregnancy following evidence of mating.

Gestation: There were no differences in gestation length. The distribution for treated females was comparable to controls.

Litter Size and Viability: No differences in corpea lutea, implantation sites, or pre- and post-implantation losses were detected for females from treated groups when compared to controls. Of the litter born, litter size at birth and subsequently on Days 1 and 4 post partum were comparable to controls.

Offspring Growth and Development: No differences in litter weights, offspring weights or surface righting were detected for litters from treated groups when compared to control litters.

Litter Observations: No clinically observable signs of toxicity were detcted for offspring from all treatment groups.

Pathology:

Organ wieghts: No toxicologically significant effects were detected in the organ weights measured.

Necropsy:There were no toxicilogically significant macroscopic abnormalities detected.

Histopathology: There were no treatment-related microscopic effects detected.


Short description of key information:
The study was desgined to investigate the systemic toxicity and potential adverse effects on reproduction (including offspring development) of the test item and complies with the recommendations of the OECD Guidelines for Testing of Chemicals No. 421 "Reproduction/Developmental Toxicity Screening Test" (adopted 27 July 1995).

The study has been ranked reliability 1 according to the scoring system by Klimisch et al. This ranking was deemed appropriate as the study was conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

Effects on developmental toxicity

Description of key information
The study was desgined to investigate the systemic toxicity and potential adverse effects on reproduction (including offspring development) of the test item and complies with the recommendations of the OECD Guidelines for Testing of Chemicals No. 421 "Reproduction/Developmental Toxicity Screening Test" (adopted 27 July 1995).
The study has been ranked reliability 1 according to the scoring system by Klimisch et al. This ranking was deemed appropriate as the study was conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.
Additional information

Introduction: The study was desgined to investigate the systemic toxicity and potential adverse effects on reproduction (including offspring development) of the test item and complies with the recommendations of the OECD Guidelines for Testing of Chemicals No. 421 "Reproduction/Developmental Toxicity Screening Test" (adopted 27 July 1995).

Methods: The test item was administered by gavage to three groups each of ten male and ten female Wistar Han TM: WIST strain rats, for up to fifty four days, at dose levels of 100, 300 and 1000 mg/kg/day. A control group of ten males and ten females were dose with vehicle alone. (Arachis oil).

Clinical signs, body weight development, food and water consumption were monitored during the study.

Pairing of animals within each dose group was undertaken on a one male: one female basis on Day 15 of the study, to produce litters. During the lactation phase, daily clinical observations werte undertaken on all live offspring, together with litter size, offspring weights and assesment of developmental landmarks.

Males were terminated on Day 43, followed by termination of females and offspring on Day 5 post partum. All animals were subjected to a gross necropsy examination and preliminary histopathological evaluation was undertaken.

Results:

Mortality: There were no unscheduled deaths during the study.

Clinical Observations: There were no clinical signs of toxicity detected.

Body Weight: No adverse effects on body weight development were detected for all treated animals or recovery animals during the treatment free period when compared to controls.

Food Consumption:No adverse effects on food intake or food efficiency were detected.

Water Consumption: No intergroup differences were detected.

Reproductive Performance:

Mating:

There were no toxicologically significant effects on mating or conception rates for animals of either sex treated with 100, 300 or 1000 mg/kg/day.

One females treated with 1000 mg/kg/day and one females treated with 100 mg/kg/day failed to achieve pregnancy following evidence of mating.

Gestation: There were no differences in gestation length. The distribution for treated females was comparable to controls.

Litter Size and Viability: No differences in corpea lutea, implantation sites, or pre- and post-implantation losses were detected for females from treated groups when compared to controls. Of the litter born, litter size at birth and subsequently on Days 1 and 4 post partum were comparable to controls.

Offspring Growth and Development: No differences in litter weights, offspring weights or surface righting were detected for litters from treated groups when compared to control litters.

Litter Observations: No clinically observable signs of toxicity were detcted for offspring from all treatment groups.

Pathology:

Organ wieghts: No toxicologically significant effects were detected in the organ weights measured.

Necropsy:There were no toxicilogically significant macroscopic abnormalities detected.

Histopathology: There were no treatment-related microscopic effects detected.

Justification for classification or non-classification

The submission substance did not meet the criteria for classification as regards impairing fertility or reproduction, or causing harm to the unborn child.