Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted according to OECD 402 and GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
dd February 24, 1987
Deviations:
yes
Remarks:
At 2 days during study, the temperature was not recorded continuously. Only 2 dose groups i.o. 3 as required. These deviations had no apparant effect on the study outcome.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: White crystals, homogeneous
- Analytical purity: 98%
- Impurities (identity and concentrations):
Trimethylamine 0.05%
Trimethylamine hydrochloride 0.05%
Iron 0.15ppm
Potassium 0.15ppm
Potassium + sodium 0.454ppm
Sodium 0.304ppm
Water 0.12%
- Purity test date: 02/11/2007
- Lot/batch No.: DEZ5-42
- Expiration date of the lot/batch: not described
- Stability under test conditions: stable
- Storage condition of test material: Room temperature and humidity

Test animals

Species:
rabbit
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Millbrook Breeding Labs, Amherst, MA, USA
- Age at study initiation: 11-13 weeks
- Weight at study initiation: 2.5-2.8 kg for males and 2.4-2.8 kg for females
- Fasting period before study: no
- Housing: individually, suspended wire cages
- Diet: fresh PMI Rabbit Chow (Diet # 5321), ad libitum
- Water: ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): "temperature controlled"
- Humidity (%): not described
- Air changes (per hr): not described
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 05/31/07 To: 07/04/07

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: approximately 10% of the body surface
- Type of wrap if used: exposed area was covered with surgical gauze patch and torso was wrapped with plastic in a semi-occlusive manner.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with tap water/ distilled water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 500/200 mg/kg
- For solids, paste formed: yes, the test article was moistened with 0.4 to 1.4 ml of distilled water to form a paste.
Duration of exposure:
24 hours
Doses:
200 or 500 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of weighing: pretest, weekly and at death
- Frequency of observations: twice daily for mortality
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs( 1,2, and 4 hours postdose and once daily for 14 days); iritation scoring: 24 hrs, 7 and 14 days post dose
Statistics:
An estimate of the LD50 was made based on the survival during the study.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 200 - < 500 mg/kg bw
Based on:
test mat.
Mortality:
At 500 mg/kg bw, 6/10 animals died (4M + 2F). Deaths occurred within 22 hours post dose. All animals survived the 200 mg/kg bw dose.
Clinical signs:
Pre-death physical signs included lethargy and wetness of the nose/mouth area. Instances of wetness of the nose/mouth area, lethargy, few feces and diarrhea were noted in the survivors. Dermal effects were absent throughout the study at 500 mg/kg bw.
At 200 mg/kg, instances of diarrhea, few feces and soiling of the anogenital area were noted during the study. Dermal effects ranged from absent to very slight on day 1 and were absent on days 7 and 14 (only seen in 2/5 males, absent in females).
Body weight:
Body weight changes were normal.
Gross pathology:
Necropsy results of the animals that died after exposure revealed wetness of the nose/mouth area and abnormalities of the treated skin area, lungs, intestines, spleen, thymus and pancreas. Necropsy of the surviving animals revealed abnormalities of the thymus and kidneys among three of the animals; one survivor appeared normal at necropsy.
At 200 mg/kg, necropsy showed abnormalities of the kidneys in one animal. All other animals appeared normal.

Applicant's summary and conclusion

Conclusions:
The dermal LD50 of the test compound was found to be >200 mg/kg but less than 500 mg/kg of body weight.
Executive summary:

An acute dermal toxicity test was performed according to current OECD guidelines and under GLP principles. Rabbits were exposed to 200 or 500 mg/kg bw. After exposure to the highest dose, 6/10 animals died. No mortality was seen after exposure to 200 mg/kg bw. Lethargy, instances of diarrhea, few feces and soiling of the anogenital area were noted during the study. Dermal effects ranged from absent to very slight on day 1 and were absent on days 7 and 14 (only seen in 2/5 males, absent in females). Changes in weight gain were absent throughout the study.

The dermal LD50 of the test compound was found to be >200 mg/kg but less than 500 mg/kg of body weight. Based on these data, the substance has to be classified for dermal toxicity in category 3 according to CLP Regulation (EC) 1272/2008.