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Description of key information

Acute oral toxicity
The LD50 in female Wistar rats after a single oral application of the similar supporting substance C20-22-alkyltrimethylammonium chloride was 3190 mg/kg bw.
Acute dermal toxicity:
In a weight-of-evidence approach data on acute dermal toxicity of similar substances were used together with information on dermal absorption and taking into consideration the low acute oral toxicity of the substance. From this combined evidence it can be concluded that the acute dermal toxicity is >2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1972-1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given: comparable to OECD TG 401. For Justification for read-across see chapter 1 of the chemical safety report.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Acute oral toxicity after single application. Test performed before OECD and GLP guidelines. Important aspects (14 day-postobservation time) in line with current OECD guidelines.
GLP compliance:
no
Remarks:
performed before GLP guidelines
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hoechst
- Age at study initiation: no data
- Weight at study initiation: 82-104 g (mean 93 g )
- Fasting period before study: 16 h
- Housing: in plastic cages
- Diet (e.g. ad libitum): Standard Altromin R, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS: no data
Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10 %
- Amount of vehicle (if gavage): dependent on dose, not constant
- Justification for choice of vehicle: not given

MAXIMUM DOSE VOLUME APPLIED: 50 ml/kg
Doses:
800 mg/kg
1250 mg/kg
2000 mg/kg
3200 mg/kg
5000 mg/kg
No. of animals per sex per dose:
10 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing once per week
- Necropsy of survivors performed: unclear from report
- Other examinations performed: body weight, no further information
Statistics:
LD50 was calculated using Probit analysis
Preliminary study:
No sex differences were observed in preliminary study, therefore only females were used in the main study
Sex:
female
Dose descriptor:
LD50
Effect level:
3 190 mg/kg bw
Mortality:
The following number of deaths were observed per dose group:
dose (mg/kg) -- number of death animals -- number of total animals
800 -- 0 -- 10
1250 -- 0 -- 10
2000 -- 1 -- 10
3200 -- 5 -- 10
5000 -- 10 -- 10
Clinical signs:
not reported
Body weight:
body weights are reported but results were not analysed or commented
Gross pathology:
unclear if done
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 in female Wistar rats after a single oral application of the surrogate substance was 3190 mg/kg bw.
Executive summary:

Acute oral toxicity of a supporting substance was determined in a study similar to OECD TG 401 (pre-GLP, RL2). The LD50 in female Wistar rats after a single oral application of the supporting substance was 3190 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
3 190 mg/kg bw
Quality of whole database:
Sufficient.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
mg/kg bw
Quality of whole database:
(LD50 >2000 mg/kg.) Sufficient.

Additional information

Acute oral toxicity of the similar surrogate substance C20-22-alkyltrimethylammonium chloride, which differs from the submission substance only by the anion, was determined comparable to OECD TG 401. The LD50 in female Wistar rats after a single oral application of the supporting substance was 3190 mg/kg bw.

This LD50 value is considered to apply for the submission substance as well.

No reliable information is available for acute inhalative toxicity.

Published data on related substances concerning acute dermal toxicity is available.

In a weight-of-evidence approach, five studies were considered:

In an acute dermal toxicity study in male and female rabbits with didecyldimethyl ammonium chloride, the combined LD50 (male/female) was 2930 mg/kg bw.

In an acute dermal toxicity study in male and female rabbits with tallowalkyltrimethyl ammonium chloride the combined LD50 was <4.0 ml/kg bw; at the only dose tested 100% mortality was observed.

In an acute dermal toxicity study in male and female rabbits with tallowalkyltrimethyl ammonium chloride the combined LD50 was <4.7 ml/kg bw; at the only dose tested 5 of 6 animals died.

In an acute dermal toxicity study in male and female rabbits with Hexadecyltrimethylammonium chloride the combined LD50 was ca. 4300 mg/kg bw. 3 of 6 animals died at the only dose administered.

Additionally, dermal absorption data on the related substance C22-alkyltrimethylammonium chloride is reported in 7.1.2 (OECD TG 428 study). The maximum dermal absorption percentage reported is 0.20 +/- 0.20% of the applied dose (contained in a formulation). Therefore, it is reasonable to assume that the acute dermal toxicity of C22-alkyltrimethylammonium chloride is well below the acute oral toxicity reported above. Data on C22-alkyltrimethylammonium chloride is considered relevant for the submission substance, as it differs from the submission substance only by the purity and another anion.

Evaluating all the information above, the submission substance is considered to have an acute dermal LD50 > 2000 mg/kg bw.

Additional data on related substances is also available, which supports the conclusion above:

In a acute dermal toxicity study in rabbits with didecyldimethyl ammonium chloride, the LD50 was 3342 mg/kg bw.

In an acute dermal toxicity study in male and female rabbits with didecyldimethyl ammonium chloride (purity: 65%), the combined LD50 was 4350 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
Reliable study for surrogate substance.

Justification for selection of acute toxicity – dermal endpoint
Weight-of-evidence; several study records.

Justification for classification or non-classification

Due to available data on the substance most similar to the submission substance (the analogue substance C20-22-alkyltrimethylammonium chloride differs from the submission substance only by the anion), with an LD50 oral in rats of 3190 mg/kg bw, the submission substance does not have to be classified as acute orally toxic according to the criteria laid down according to Regulation (EC) No 1272/2008.

Data available on acute inhalative toxicity for supporting substances of restricted reliability are contradictory and do not indicate a need to classify for acute inhalation toxicity according to Regulation (EC) No 1272/2008.

A weight-of-evidence-reflection of several studies with related substances on acute dermal toxicity and additional information on acute oral toxicity and absorption for the substance most similar to the submission substance (C20-22-alkyltrimethylammonium chloride differs from the submission substance only by the anion) lead to the conclusion that the acute dermal toxicity of the submission substance is above 2000 mg/kg bw. Therefore, the submission substance does not have to be classified for acute dermal toxicity according to Regulation (EC) No 1272/2008.

The analogue substance C20-22-alkyltrimethylammonium chloride and thus the submission substance do not have to be classified for specific target organ toxicity - single exposure according to Regulation (EC) No 1272/2008, as no specific toxic effects were reported after acute exposure.