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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was conducted according to the OECD guideline 409 as well as in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 409 (Repeated Dose 90-Day Oral Toxicity in Non-Rodents)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Test substance: ca. 50% C12-16-benzyldimethylammonium chloride (CAS no.: 68424-85-1)
in water only. Specification as in 1.1-1.4: C12-16 BKC (C12: 72.0%; C14: 27.7%; C16: 0.3%)
(batch No. 667H3002)

Test animals

Species:
dog
Strain:
Beagle
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
Continuous
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 500, 1500 and 3000 ppm of test substance in the diet. The mean achieved dosages of active substance, based on food consumption and body weight information were as follows: 0, 8, 25 and 50 mg/kg/d (males); 0, 9, 26 and 45 mg/kg/d (females)
Basis:

No. of animals per sex per dose:
4 males and 4 females per dose group
Control animals:
yes, plain diet
Details on study design:
Post-exposure period: none

Examinations

Observations and examinations performed and frequency:
Observations included: Clinical signs, mortality, body weight, food consumption, Ophthalmology, haematology, clinical chemistry and urinanalysis.
Sacrifice and pathology:
Pathology of all animals (organ weight, gross pathology) and histopathology on the control and high dose animals.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
not examined
Urinalysis findings:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Details on results:
From week 8, the concentration of test substance was reduced to 2500 ppm (equivalent to 1250 ppm of active substance) in the high-dose female group, due to low food intake. The mean achieved dosages of active substance, based on food consumption and body weight information were as follows: 0, 8, 25 and 50 mg/kg/d (males); 0, 9, 26 and 45 mg/kg/d (females).
No clinical signs were attributed to treatment with the test substance. No mortality observed. Body weight: No treatment related effects on the body weight gain were attributed to the test substance. A mean body weight loss was noted in females from the high-dose group when given 3000 ppm of test substance. This body weight loss was not dose-related and correlated to the decrease of food consumption recorded among the females of that dose group. When the dosing was reduced to 2500 ppm of test substance, a mean body weight gain, similar to that noted in the control females was recorded. Consequently, this effect was associated with the low appetency of the diet at this dose-level.
Food consumption: In the 500 and 1500 ppm dose group, the food consumption was unaffected in males and females. A markedly lower (-27%) food consumption was noted in females at the high dose group of 3000 ppm. After reduction of the dose-level to 2500 ppm test substance, the food consumption was only slightly lower (-6%). No effects seen at ophthalmoscopic examination, haematology, clinical chemistry and urine analysis.
No treatment-related effects on organ weights were noted. Gross and histopathology showed no findings.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
50 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
male
Basis for effect level:
other: No toxicologically significant effect; 1500 ppm (male) and 1250 ppm (female) were corresponding to 50 and 45 mg a.i./kg/d, respectively.
Dose descriptor:
NOAEL
Effect level:
45 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
female
Basis for effect level:
other: No toxicologically significant effect; 1500 ppm (male) and 1250 ppm (female) were corresponding to 50 and 45 mg a.i./kg/d, respectively.
Dose descriptor:
LOAEL
Effect level:
>= 50 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Under the condition of the study, the 90-d NOAEL for systemic effects in Beagle dogs was established at the highest tested dose of 1500 or 1250 ppm active substance in males and females, respectively (i.e., corresponding to 50 or 45 mg a.i./kg bw/d, respectively).
Executive summary:

A guideline compliant 90 day dietary study in Beagle dogs was conducted at doses of 0, 500, 1,500 and 3,000 ppm (corresponding to 0, 250, 750 or 1,500 ppm of active substance). Four males and 4 females per dose group were used. From Week 8, the concentration of test substance was reduced to 2,500 ppm (1,250 ppm of active substance) in the high-dose female group, due to low food intake. The mean achieved dosage of active substance, based on food consumption and body weight were 0, 8, 25 and 50 mg/kg bw/day (males); 0, 9, 26 and 45 mg/kg bw/day (females). No treatment-related toxicologically significant effect was observed up to the highest tested dose. A mean body weight loss observed in females from the high-dose group (3,000 ppm) was not dose-related and correlated to the decrease of food consumption recorded among the females of that dose group. When the dosing was reduced to 2,500 ppm of test substance, a mean body weight gain, similar to that noted in the control females was recorded. Consequently, this effect was associated with the reduced palatability of the diet at this dose-level. Under the conditions of the study, the 90-day NOAEL for systemic effects in Beagle dogs was established at the highest tested dose of 1,500 or 1,250 ppm active substance in males and females, respectively (i.e., corresponding to 50 or 45 mg a.i./kg bw/day, respectively) (Guilaumat P-O, 2006).