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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been presented to ECHA in the framework of a NONS notification. The document is now public because presented more than 12 years ago.
Qualifier:
according to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
water
Frequency of treatment:
daily, 7 days a week
No. of animals per sex per dose:
Male: 8 animals at 40 mg/kg bw/day
Male: 8 animals at 200 mg/kg bw/day
Male: 16 animals at 1000 mg/kg bw/day
Female: 8 animals at 40 mg/kg bw/day
Female: 8 animals at 200 mg/kg bw/day
Female: 16 animals at 1000 mg/kg bw/day
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
at the high and medium dose
Food consumption and compound intake (if feeding study):
no effects observed
Ophthalmological findings:
effects observed, treatment-related
Description (incidence and severity):
blue discoloration of the eye at the highest dose
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
only at the high dose
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
only at the hogh dose(male)
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
blue discolouration
Histopathological findings: non-neoplastic:
no effects observed
Dose descriptor:
NOAEL
Effect level:
ca. 200 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical biochemistry
clinical signs
gross pathology
Critical effects observed:
not specified

MORTALITY AND CLINICAL SIGNS

The animals from the high-dose group exhibited a bluish discoloration of the faeces, skin and eyes. Blue discoloration of the skin was observed up to the 12th day, the blue discoloration of the eyes was not reversible. Up to the end of the treatment period a (non-significant) reduced body weight was observable among the male animals from the medium and high-dose groups. The body-weight gain was temporarily (on day 16) significantly reduced in both of the dose groups. The feed consumption of the treated animals did not differ from that found in the controls.

CLINICAL CHEMISTRY

Clinico-chemically, increased total cholesterol and phospholipid values as well as increased ASAT activity were revealed for the male animals from the high-dose group. Among the female animals, the alpha-1-globulin values were elevated. At the end of the follow-on observation period, these clinico-chemical values were located within the normal range once more.

GROSS PATOLOGY

At the high dose, at the end of treatment, reduced absolute and relative thymus weights were determined in both of the sexes. At the end of the follow-on observation period, increased relative thymus weights occurred among the high-dose males. Post-mortem examination revealed blue discoloration of the kidneys (in particular in the case of the cortex region) in all of the treated animals as well as blue discoloration of the mesenteric lymph nodes and testes of numerous animals from the medium and high-dose groups. Discoloration, which was still present in the majority of the organs at the end of the follow-on observation period, but not, however, in the thymus, tongue and intestines, was also observed in other organs (salivary glands, thymus, mandibular lymph nodes, tongue, stomach, small intestine, large intestine, pancreas, epididymides, ovaries, uterus, subcutis). One male from each of the dose groups as well as a high-dose female additionally exhibited blue discoloration of the lung.

Microscopically, eosinophilic inclusions in the tubular epithelia were determined in almost all of the males from all of the dose groups and from the control. At the high dose, the severity of this finding was greater than in the case of the controls. After the recovery period no difference was detected in the frequency or the degree of severity of these findings. No further treatment-related, pathohistological changes were established in the macroscopically discoloured organs. The eyes, brain, spinal marrow and peripheral nerve were examined histologically in the control and high-dose group. They did not exhibit any treatment-related changes.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
200 mg/kg bw/day
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification