Didecyldimethylammonium chloride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 May, 1996 - 12 June, 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Didecyldimethylammonium chloride

EC Number:

230-525-2

EC Name:

Didecyldimethylammonium chloride

Cas Number:

7173-51-5

Molecular formula:

C22H48N Cl

IUPAC Name:

didecyldimethylammonium chloride

Details on test material:

The test substance contains ca. 50% didecyldimethylammonium chloride (CAS no.: 7173-51-5) and 20% isopropanol (CAS no.: 67-63-0) in
water.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Species: Rat
Strain: Wistar strain Crl:(WI) BR (outbred, SPF-quality)
Source: Charles River, Sulzfeld, Germany.
Sex: Males and females
Age/weight at study initiation: Approx. 9 weeks, 373 g (mean males) and 240 g (mean females)
Number of animals per group: 5 males and 5 females
Control animals: No

Administration / exposure

Vehicle:

water

Details on dermal exposure:

Postexposure period: 15 days
Type: Dermal
Concentration: 2000 mg/kg bw for 24 hours (dose volume: 10 ml/kg in distilled water)
Vehicle: Distilled water
Concentration in vehicle: 200 mg/ml (20%)
Total volume applied: 10 ml/kg
Controls: No

Doses:

Limit test at 2000 mg/kg bw.

No. of animals per sex per dose:

10

Control animals:

no

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 000 mg/kg bw

Based on:

act. ingr.

Clinical signs:

other: Lethargy was noted in all animals, between days 2 and 4. Hunched posture was observed in four females between days 2 and 6. Skin effects in the treated area: Swelling, necrosis and hardening of the back, scabs and brown skin on the back were noted in all

Gross pathology:

No abnormalities were found at macroscopic post mortem examination Of the animals.

Other findings:

At removal of the bandages (day 2) it was noticed that the bandages of two Females (number 9 and 10) had shifted caudally. The clinical signs shown by these animals were not significantly different compared to the other females. The exposure to the test substance was therefore considered sufficient.

Any other information on results incl. tables

No mortality occurred. Effects noted were lethargy in all animals between day 2 and 4 and skin effects which consisted
of swelling, redness, erythema and necrosis of the skin. The majority of the skin effects persisted until the end of the
observation time. No abnormalities were found at macroscopic post mortem examination.

Applicant's summary and conclusion

Interpretation of results:

other: Category 4 based on EU CLP criteria

Conclusions:

The acute dermal LD50 of the test substance in rats was determined to be >2000 mg/kg bw (i.e. >1000 mg a.i./kg bw).

Executive summary:

A study performed according to GLP and OECD 402 and EU B.3 “Acute Dermal Toxicity”. Five male and five female rats received a dermal dose of 2000 mg/kg bw for 24 h (dose volume: 10 ml/kg in distilled water) under occlusive dressing for 24 h. One day before exposure (day -1) an area of approximately 5x7 cm on the back of the animal was clipped. 24 h, after which dressings were removed and residual test substance removed using a tissue moistened with tap water. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice on day 15. No mortality occurred. Effects noted were lethargy in all animals between day 2 and 4 and skin effects which consisted of swelling, redness, erythema and necrosis of the skin. The majority of the skin effects persisted until the end of the observation time. No abnormalities were found at macroscopic post mortem examination. Effects are limited to local irritation/corrosion of the skin, without involvement of systemic toxicity. The acute dermal LD50 of the test substance in rats were determined to be >2000 mg/kg bw (i.e. >1000 mg a.i./kg bw).

As quaternary ammonium compounds do not easily pass biological membranes, dermal absorption of these compounds is very limited. The dermal toxicity of aqueous DDAC solutions is related to its corrosivety and therefore more related to the concentration of the administered solution then of the actual amount in mg/kg. Due to the direct corrosive effect, there is danger of irreversible damage to the skin upon exposure to the undiluted solution. Further toxicity is secondary to the local tissue damage, rather than the result of percutaneously absorbed material. Some reviews mention comparable dermal LD₅₀ data in rat from literature which is in the range 2000 – 3000 mg/kg bw.

Toxicity is related to concentration dependent cytotoxicity, with a lack of specific systemic toxicity. The toxicity (and efficacy as based on same mechanism of action) show a dependence on chain length, with an optimum at C₁₀-C₁₂. Therefore this test using C₁₀-chainlength can be seen as worst case representative for the whole group of DDAC compounds between C₈ and C₁₈. Furthermore, additional tests for acute dermal toxicity are not ethical due to its corrosive effects and can thus not be performed.