Benzyldimethyl(octadecyl)ammonium chloride

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Cross-reference

Cross-reference 1

Reference

Endpoint:

appearance / physical state / colour

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From December 06, 2017 to December 06, 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.6302 (Color)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.6303 (Physical State)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.6304 (Odor)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Identity: Benzyldimethyl(octadecyl)ammonium chloride
Batch no: 14217
Content: Cationic activity 97.6%
Expiry date: 06/2019
Storage conditions: Room temperature, protect from humidity and water

Physical state at 20°C and 1013 hPa:

solid

Key result

Form:

solid

Colour:

White

Odour:

sweetish

Substance type:

organic

Conclusions:

Under the study conditions, the test substance is a white solid with sweetish odour at ambient temperature.

Executive summary:

A study was conducted to determine the physical state, color and odour of the test substance, C18 ADBAC (active: 97.6%), according to the OCSPP Guidelines 830.6302, 830.6303 and 830.6304, in compliance with GLP. Under the study conditions, the test substance is a white solid with sweetish odour at ambient temperature (Wannenwetsch, 2017).

Cross-reference 2

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

The vapour pressure of the test substance was determined using the static method, according to EU Method A.4, (Chilworth, 2017) as well using three QSAR i.e., EPI Suite v.4.11, US EPA T.E.S.T (US EPA, 2018) and ChemProp (UFZ, 2018).

Vapour pressure:

0 Pa

at the temperature of:

25 °C

In absence of a reliable experimental study with the test substance, the vapour pressure (VP) endpoint has been assessed based on the below weight of evidence:

- Experimental VP = 6.6 Pa at 20 °C; the measured VP value is considered to be reliable with restrictions, as it can be suspected to be influenced by trapped gas/solvent/impurities.

- Estimated VP = 1.59E-11 Pa at 25°C (using modified grain method of EPI Suite v.4.11 program); 7.38E-7 at 25°C (using consensus method of T.E.S.T. v.4.2.1); the estimates are considered to be reliable with restrictions, as they do not completely fall within of the applicability domain. Also, the two QSAR models are not powered enough to predict ionic substances. Therefore the VP was estimated using a third QSAR model, ChemProp v.6.0, which resulted in VP values 5.75E-5 Pa and 1.12E-7 Pa at 25°C using modified Grain Antoine and modified Grain Watson methods respectively.

- Experimental VP of structurally similar substance, C12-16 ADBAC: 1.5E-03 Pa at 20°C and 1.58E-3 Pa at 25°C (ECHA REACH dossier; EC: 939-253-5).

Overall, based on the available weight of evidence, the test substance can be considered to have low volatility. However, in absence of a reliable experimental value, the higher QSAR based VP value (i.e., 5.75E-5 Pa) at25°C has been considered further for hazard/risk assessment.

Cross-reference 3

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2006

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

KL2 due to RA

Justification for type of information:

Refer to the section 13 of IUCLID dataset for details on the read across justification. The algae study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 409 (Repeated Dose 90-Day Oral Toxicity Study in Non-Rodents)

Deviations:

no

GLP compliance:

yes

Limit test:

no

Species:

dog

Strain:

Beagle

Sex:

male/female

Route of administration:

oral: feed

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

Continuous

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 bw/day (males); 0, 9, 26 and 45 mg/kg bw/day (females).

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

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.

Clinical signs:

no effects observed

Description (incidence and severity):

No clinical signs were attributed to treatment with the test substance.

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

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 and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

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.

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

not examined

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

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 bw/day (males); 0, 9, 26 and 45 mg/kg bw/day (females).

Key result

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/ bwday, respectively.

Key result

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 bw/day, respectively.

Key result

Critical effects observed:

no

Conclusions:

Based on the results of the study, the 90 d NOAEL for systemic effects in Beagle dogs is considered to be at the highest tested dose of 1500 or 1250 ppm a.i. in males and females, respectively (i.e., corresponding to 50 and 45 mg a.i./kg bw/d, respectively)

Executive summary:

A 90-d study was conducted to determine the repeated dose oral toxicity of the read across substance, C12-16 ADBAC (active: 50%) in Beagle dogs, according to OECD Guideline 409, in compliance with GLP. In this study, the test substance was administered to 4 animals per sex per group at dietary concentrations of 0, 500, 1500 and 3000 ppm (equivalent to 0, 250, 750 or 1500 ppm a.i.). From Week 8, the concentration of test substance was reduced to 2500 ppm (1250 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 a.i./kg bw/d for males and 0, 9, 26 and 45 mg a.i./kg bw/d for females. No treatment-related toxicologically significant effects were observed up to the highest tested dose. A mean body weight loss observed in females from the high dose group 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 reduced palatability of the diet at this dose level. Under the conditions of the study, the 90 d NOAEL for systemic effects in Beagle dogs was considered to be at the highest tested dose of 1500 or 1250 ppm a.i. in males and females, respectively (i.e., corresponding to 50 and 45 mg a.i./kg bw/d, respectively) (Guillaumat, 2006). Based on the results of the read across study, similar NOAEL for systemic effects can be considered for the test substance, C18 ADBAC, in 90-d repeated dose oral toxicity in dogs.