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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted according to OECD guideline, no GLP; (GLP was not mandatory when study was done)

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1981-05-12)
Deviations:
yes
Remarks:
limit dose level: 400 mg/kg bw (recommended dose level by guideline 2000 mg/kg bw)
GLP compliance:
no
Remarks:
(GLP was not mandatory when study was done)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): N,N,N',N'-Tetramethyl-1,6-hexanediamine
- Analytical purity: 97.5 %
- Expiration date of the lot/batch: 1983-11
- Impurities (identity and concentrations): N,N',N'-Trimethyl-1,6-hexanediamine 2%

Test animals

Species:
rabbit
Strain:
Vienna White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gaukler, Offenbach, Germany
- Weight at study initiation: mean (females): 2.74 kg, mean(males): 3.16 kg
- Housing: individual animals in steel cages, floor area 40 x 51 cm, no bedding
- Diet (e.g. ad libitum): Ovator Solikanin 4mm; Muskator-Werke Düsseldorf, Germany (about 130 g per day)
- Water (e.g. ad libitum): 250 ml per animal per day, fully demineralized water at workday, on other days: tap water
- Acclimation period: about 8 days before study begin, same housing conditions as during the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20- 26
- Humidity (%): 30- 70
- Air changes (per hr): 15- 20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure:395 cm^2
- Type of wrap if used: inert foil

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washing with warm water
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Concentration (if solution): 30%




Duration of exposure:
24 hrs
Doses:
400 mg/kg bw
No. of animals per sex per dose:
5 female and 5 male animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: signs and symptoms were recorded several times on day of application and then once per workday. Check for moribund and dead animals twice each workday and once on other days. Check for skin was done 30-60 minutes after removal of occlusive dressing and then each workday. Weighing was done immediately after beginning of the test and after 4, 7, 11 and 15 days
- Necropsy of survivors performed: yes
- Other examinations performed: organ weights, histopathology

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 400 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 0/5 male animals died; 2/5 female animals died after 8 d
Sex:
male
Dose descriptor:
LD50
Effect level:
> 400 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no male animals died
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 400 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 2/5 female animals died
Mortality:
male animals: 0/5 died
female animals 2/5 died after 8 days
Clinical signs:
male animals: apathy from day 1 to 11

female animals: dyspnea at day 4
apathy: from day 1 to day 8
abnormal position, diarrhoe: at day 4
Body weight:
For all surviving animals body weight gain was normal or as expected. One animal that died at day 8 showed reduced body weight after 4 days (-15%)
Gross pathology:
Animals that died (females):
Skin: deep necrosis; general passive hyperemia
Sacrificed animals (males and females):
Skin: deep necrosis at the application site with callous thickening of the subcutis and edematization of the muscles
Organs: no abnormalities detected
Other findings:
local findings on male and female animals:
erythema: from day 1 to 6
deep necrosis: from day 1 to 15
edema: from day 1 to 15

Any other information on results incl. tables

Table 1: Mortality

Dose [mg/kg bw]

Toxicological
results*

mortality

Males

400

0/5

0%

Females

400

5/5

20%

LD50 > 400 mg/kg bw

* first number = number of dead animals,
second number = number of animals used

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance is classified for acute dermal toxicity in Category 3 (CLP); toxicity is attributable to local corrosivity.
Executive summary:

A test of acute dermal toxicity was conducted on 5 male and 5 female rabbits with the test substance. Substance was applied occlusive at a dose of 400 mg/kg bw. Test deviated from OECD guideline 402 in limitation of dosage to 400 mg/kg bw and the occlusive application. After 8 days 2/5 female animals died whereas all males survived. Therefore a mortality of 40% for female rabbits and 0% for male rabbits can be derived resulting in a LD50 > 400 mg/kg bw.