Reaction mass of sodium 4-chloro-5-alkylbenzotriazolide and sodium 5-chloro-4-alkylbenzotriazolide and sodium 4-chloro-7-alkylbenzotriazolide and sodium 5-chloro-6-alkylbenzotriazolide

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

See attachment

Limit test:

no

Test material

Test material information

Constituent 1

Test animals

Species:

rat

Strain:

CD-1

Sex:

male/female

Details on test animals or test system and environmental conditions:

Age : 26 - 30 days
Male weight: 72 - 78 g
Female weight: 70 - 83 g
Acclimatisation period: 8 days
Room temperature: 19 - 23°C
Relative humidity: 40 - 70 %

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

other: 1% w/v methylcellulose in purified water

Duration of treatment / exposure:

Test duration: 28 days

Frequency of treatment:

Dosing regime: once a day

No. of animals per sex per dose:

Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 15 mg/kg bw/day
Male: 5 animals at 150 mg/kg bw/day
Male: 5 animals at 1000 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 15 mg/kg bw/day
Female: 5 animals at 150 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day

Examinations

Observations and examinations performed and frequency:

Clinical signs once a day
Neurobehavioural screening once a day
Body weight twice a week
Food consumption weekly
Water consumption daily

Sacrifice and pathology:

Clinical pathology: removal of blood samples, haematology, biochemistry
Terminal studies: organ weight, macroscopic pathology, microscopic pathology

Statistics:

Food consumption
body weight gain
organ weight
clinical pathology

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

no effects observed

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Details on results:

Clinical observations:
There were no deaths. Salivation, occurring immediately after dosing, was observed in the majority of male and female rats receiving 1000 mg/kg/day during the 4 week period. On isolated occasions among a few high dose level animals, salivation persisted for up to 30 minutes after dosing. Salivation was occasionally present in some animals receiving 150 mg/kg/day.

Brown perioral staining and wet coat, both associated with post dosing salivation, occurred infrequently among some high dose level animals during the 4 week treatment period.

Other findings consisted of paddling motions of the forepaws, which occurred frequently among both sexes treated with 1000 mg/kg/day. Walking on toes also occurred on occasions during the treatment period in females and, to a lesser extent among some males receiving 1000 mg/kg/day.
This finding persisted for up to 30 minutes after treatment.

Treatment with the test substance was not associated with any behavioural changes which were considered indicative of neurotoxicity.

Bodyweight gain, food and water consumption were all considered to have been unaffected by treatment with the test substance.

Laboratory findings:
Several biochemical and haematological parameters were slightly altered but values generally fell within historical control ranges. No findings of toxicological significance occured.

Effects in organs:
No treatment-related findings occured.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

> 1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

2

Dose descriptor:

NOEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Classified as: Not classified under EU regulation