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Description of key information

Repeated Dose Toxicity: Oral Route

Under the conditions of the study, the No-Observed-Adverse-Effect-Level (NOAEL) was considered to be 1000 mg/kg/day.

Repeated Dose Toxicity: Inhalation Route

In accordance with Section 8.6.1. of Column 2 of Annex VIII of the REACH Regulation, Short-term repeated dose toxicity study (28 days) should be conducted on one species, male and female, through the most appropriate route of administration, having regard to the likely route of human exposure which in this case is the oral route.

Repeated Dose Toxicity: Dermal Route

In accordance with Section 8.6.1. of Column 2 of Annex VIII of the REACH Regulation, Short-term repeated dose toxicity study (28 days) should be conducted on one species, male and female, through the most appropriate route of administration, having regard to the likely route of human exposure which in this case is the oral route.

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
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The study was performed in accordance with standardised guidelines and under GLP conditions. The study was assigned a reliability score of 1 in line with the principles for assessing data quality as defined by Klimisch et al. (1997). The quality of the database is therefore considered to be good.

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

14 Day Range-finding study: Oral Route

The purpose of this study was to assess the systemic toxic potential of the test material in a range finding study by oral gavage administration to Han Wistar rats for 14 days.

The doses selected for this study were 100, 300 and 1000 mg/kg/day. During the study, clinical condition, body weight, food consumption, water consumption, organ weight and macropathology investigations were undertaken. During the study, body weight, food consumption, organ weight and macropathology investigations were undertaken.

There were no clinical signs or dosing observations considered related to treatment with the test material at 100, 300 or 1000 mg/kg/day, and no deaths occurred on study.

The bodyweight, bodyweight change and food consumption of males was considered unaffected by treatment with at 300 or 1000 mg/kg/day from Days 1-15 of treatment when compared with that of males receiving 100 mg/kg/day. Body weight gain and food consumption of females receiving 1000 mg/kg/day were higher than in females receiving 100 mg/kg/day, and body weight gain was slightly high among females receiving 300 mg/kg/day.

Absolute and adjusted mean liver weights were marginally higher amongst males and females which received the test material at 1000 mg/kg/day, and males receiving 300 mg/kg/day, when compared with the liver weights of males and females which received the test material at 100 mg/kg/day.

There were no findings considered to be related to treatment with the test material. It was considered that a high dose of 1000 mg/kg/day would be appropriate for the upcoming 4-week study. The proposed low and intermediate doses are 100 and 300 mg/kg/day, respectively.

Under the conditions of the study, there were no findings considered to be related to treatment with the test material up to 1000 mg/kg bw.

Repeated Dose Toxicity: Oral Route

The potential for the test material to cause repeated dose toxicity was investigated in a GLP study conducted in accordance to the standardised guidelines OECD 407, EU method B7, OPPTS 870.3050 and Japanese guidelines YAKUSHOKUHATSU No. 0331. 7, SEIKYOKU No. 5 and KANPOKIHATSU No.110331009.

Three groups, each comprising five male and five female RccHan™WIST rats, received the test material at doses of 100, 300 or 1 000 mg/kg/day for 28 consecutive days. A similarly constituted control group received the vehicle, corn oil, at the same volume dose as the treated groups. A further five male and five female rats were assigned to each of the control and high dose groups. These animals were treated for four weeks, followed by a two-week period without treatment to assess the potential for any treatment-related change to recover.

During the study, clinical condition, detailed physical and arena observations, sensory reactivity, grip strength, motor activity, body weight, food consumption, hematology (peripheral blood), blood chemistry, urinalysis, organ weight, macropathology and histopathology investigations were undertaken.

There were no signs associated with dosing or clinical signs at weekly physical examination and no findings at the sensory reactivity, grip strength or motor activity assessments. There was no toxicologically significant effect upon body weight, and food or water intake.

There were no toxicologically significant findings at the hematology, blood chemistry and urinalysis investigations performed in Week 4.

There was no treatment-related effect on organ weights and no treatment-related macroscopic or microscopic findings after 4 weeks of treatment or following 2 weeks of recovery.

It is concluded that oral administration of the test material to Han Wistar (RccHan™;WIST) for 4 weeks at dosages up to 1000 mg/kg/day was well tolerated with no adverse effect of treatment. Consequently, the No-Observed-Adverse-Effect-Level (NOAEL) was considered to be 1 000 mg/kg/day.

Repeated Dose Toxicity: Inhalation Route

In accordance with Section 8.6.1. of Column 2 of Annex VIII of the REACH Regulation, Short-term repeated dose toxicity study (28 days) should be conducted on one species, male and female, through the most appropriate route of administration, having regard to the likely route of human exposure which in this case is the oral route.

Repeated Dose Toxicity: Dermal Route

In accordance with Section 8.6.1. of Column 2 of Annex VIII of the REACH Regulation, Short-term repeated dose toxicity study (28 days) should be conducted on one species, male and female, through the most appropriate route of administration, having regard to the likely route of human exposure which in this case is the oral route.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance does not require classification with respect to repeated dose toxicity.