12-aminododecanoic acid

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1 December 2011 - 15 December 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No. 8147, April 2011

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

12-aminododecanoic acid

EC Number:

211-754-7

EC Name:

12-aminododecanoic acid

Cas Number:

693-57-2

Molecular formula:

C12H25NO2

IUPAC Name:

12-aminododecanoic acid

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Description: White powder
Test substance storage: In refrigerator (2 - 8 °C) in the dark
Stability under storage conditions: Stable

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Wistar, Crl:WI (Han) (outbred, SPF-quality).
- Age at study initiation: Young adult (approximately 10 weeks).
- Weight at study initiation: Bodyweight variation did not exceed ± 20 % of the sex mean.
- Fasting period before study: No.
- Housing: Individually housed in labelled cages containing sterilised sawdust as bedding material and paper as cage-enrichment.
- Diet (e.g. ad libitum): Free access to pelleted rodent diet.
- Water (e.g. ad libitum): ad libitum access to tap water.
- Acclimation period: At least 5 days, during which time the animals were group housed under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0 °C (actual range 19.7 - 21.7 °C).
- Humidity (%): 40 - 70 % (actual range 40 - 56 %).
- Air changes (per hr): Approximately 15.
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: 1 December 2011 To: 15 December 2011

Administration / exposure

Type of coverage:

occlusive

Vehicle:

CMC (carboxymethyl cellulose)

Details on dermal exposure:

TEST SITE
- Area of exposure: Approximately 25 cm² for males and 18 cm² for females. On the day prior to exposure, an area approximately 5 x 7 cm on the back of each animal was clipped.
- % coverage: Approximately 10 %.
- Type of wrap if used: The test material formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminium foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The skin was cleaned of residual test material using tap water once the dressing had been removed.
- Time after start of exposure: 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw (10 mL/kg) body weight.
- Constant volume or concentration used: yes

VEHICLE
- Vehicle: 1 % Aqueous carboxymethyl cellulose.
- Preparation: The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. No correction was made for purity of the test substance.

Duration of exposure:

24 hours

Doses:

A single dose of 2000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/viability: twice daily
Bodyweights: days 1 (prior to administration), 8 and 15
Clinical signs: at periodic intervals on day of dosing and once daily thereafter.
- Necropsy of survivors performed: yes. At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
- Clinical signs: The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1)

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred

Clinical signs:

other: Hunched posture, piloerection, chromodacryorrhoea and/or ptosis were observed for all animals. The animals had recovered from all symptoms between days 2 and 5. The results are summarised in Table 1.

Gross pathology:

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

Any other information on results incl. tables

Table 1 Summary of Clinical Signs

Animal Number	Test Day	1	1	1	2	3	4	5
	Hours After Treatment	0	2	4
Males
1	Posture     Hunched posture	-	1	1	-	-	-	-
	Secretion/excretion     Chromodacryorrhoea (Snout)	-	2	2	1	-	-	-
2	Posture     Hunched posture	-	-	-	1	-	-	-
	Skin/fur     Piloerection	-	-	1	-	-	-	-
	Secretion/excretion     Chromodacryorrhoea (Snout)	-	1	1	1	-	-	-
3	Posture     Hunched posture	-	-	-	1	-	-	-
	Secretion/excretion     Chromodacryorrhoea (Snout)	-	1	1	1	-	-	-
4	Skin/fur     Piloerection	-	-	1	-	-	-	-
	Secretion/excretion     Chromodacryorrhoea (Snout)	-	1	1	-	-	-	-
	Various     Ptosis	-	-	1	-	-	-	-
5	Posture     Hunched posture	-	-	-	1	1	1	-
	Skin/fur     Piloerection	-	-	-	1	1	-	-
	Secretion/excretion     Chromodacryorrhoea (Snout)	-	1	1	2	1	-	-
Females
6	Posture     Hunched posture	-	-	-	1	1	-	-
	Skin/fur     Piloerection	-	-	1	-	-	-	-
	Secretion/excretion     Chromodacryorrhoea (Snout)	-	1	1	-	-	-	-
7	Posture     Hunched posture	-	1	1	1	1	-	-
	Skin/fur     Piloerection	-	-	1	-	-	-	-
	Secretion/excretion     Chromodacryorrhoea (Snout)	-	2	1	1	-	-	-
	Various     Ptosis	-	-	1	-	-	-	-
8	Posture     Hunched posture	-	-	-	1	1	1	-
	Skin/fur     Piloerection	-	1	1	-	-	-	-
	Secretion/excretion     Chromodacryorrhoea (Snout)	-	1	1	-	-	-	-
9	Posture     Hunched posture	-	-	-	1	1	-	-
	Skin/fur     Piloerection	-	-	1	1	-	-	-
	Secretion/excretion     Chromodacryorrhoea (Snout)	-	1	1	-	-	-	-
10	Posture     Hunched posture	-	-	-	1	1	-	-
	Skin/fur     Piloerection	-	1	1	1	-	-	-
	Secretion/excretion     Chromodacryorrhoea (Snout)	-	1	1	1	-	-	-
	Various     Ptosis	-	-	1	-	-	-	-

Maximum grade for posture: 1

Maximum grade for skin/fur: 1

Maximum grade for secretion/excretion: 3

Maximum grade for ptosis: 3

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The dermal LD50 value of the test material in Wistar rats was established to exceed 2000 mg/kg body weight.

Executive summary:

The potential of the test material to cause dermal toxicity was investigated in Wistar rats in accordance with the standardised guidelines OECD 402, EU Method B.3, EPA OPPTS 870.1200 and JMAFF, 12 Nohsan, Notification No. 8147.

The animals were exposed to a single limit dose of the test material at 2000 mg/kg bw. No mortality or effects on bodyweight were seen and no abnormalities were observed at macroscopic postmortem examination. Clinical signs included hunched posture, piloerection, chromodacryorrhoea and/or ptosis.

The dermal LD50 value of the test material in Wistar rats was established to exceed 2000 mg/kg body weight.