Registration Dossier

Administrative data

Description of key information

In a Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening (OECD TG422) with ammonium perrhenate, treatment of rats by gavage at 330 mg/kg bw/day was associated with an increase in thyroid weight in both sexes. A slight increased incidence of ploughing and excess salivation was also noted in males at this dose level. Treatment at 110 mg/kg bw/day revealed no significant changes in any of the parameters assessed that were considered to be indicative of a reaction to treatment.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
110 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Ammonium perrhenate has good-quality data covering the skin and eye irritation, acute toxicity by the oral route, skin sensitization, and in vitro gene mutation (bacterial and mammalian cells) and cytogenicity endpoints, together with the results from this repeated dose toxicity/reproductive toxicity screen.

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

A good-quality Combined Repeated Dose Toxicity with the Reproduction/Developmental Toxicity Screening Test (OECD TG422) was conducted with ammonium perrhenate. Male and female rats were treated by gavage at 0, 110, 330 and 1000 mg/kg bw/day. Treatment at 1000 mg/kg bw/day was associated with significant toxicity, including enlarged thyroid glands and mandibular lymph nodes. Microscopic findings were noted in the thyroid and (male) pituitary glands, bone marrow, and spleen. Treatment at 330 mg/kg bw/day was associated with an increase in thyroid weight in both sexes, and a slight increased incidence of ploughing and excess salivation in males. No histological examination was undertaken at this dose level. No significant treatment-related effects were seen at 110 mg/kg bw/day. A slight increase in group mean thyroid weight when compared to Controls in males at this dose level was attributed to a single male animal with thyroid weight above the weight range observed in Controls. All other animals had thyroid weights similar to Controls and the effect in the one animal, not associated with any significant clinical findings, was not considered positively attributable to treatment and no additional histological examination was undertaken at this dose level.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Only one, good-quality study, conducted in accordance with OECD TG422 (Combined Repeated Dose Toxicity with the Reproduction/Developmental Toxicity Screening Test).

Repeated dose toxicity: via oral route - systemic effects (target organ) glandular: thyroids

Justification for classification or non-classification

There is not considered to be sufficient justification for classification for any STOT-RE (specific target organ toxicity - repeated exposure). Specific target organ toxicity covers "all significant health effects that can impair function, both reversible and irreversible, immediate and/or delayed" and classification of a substance is required if it may present a potential for adverse health effects in people who are exposed to it. For data obtained from experimental animal studies, there must be "toxicologically significant changes which have affected the function or morphology of a tissue/organ [or have produced serious changes to the biochemistry or haematology of the organism] and these changes are relevant for human health." Haematological, clinicochemical and detailed macroscopic and microscopic examination is necessary to enable the toxic effects on target tissues/organs to be identified. Changes in organ weights with no evidence of organ dysfunction or significant organ damage noted at necropsy and/or subsequently seen or confirmed at microscopic examination is not considered sufficient to support classification for specific target organ toxicity following repeated exposure.

Target organ effects (increased thyroid weight) were observed at the intermediate dose of 330 mg/kg bw/day, although no histopathology was conducted at this dose level. For results from a 28 -day repeated oral dose toxicity study in rats, classification in Category 2 for STOT-RE would be applicable when a significant toxic effect was seen to occur in the range 30< C <=300 mg/kg bw/day.