12-aminododecanoic acid

Endpoint summary

Description of key information

ORAL: LD50 = > 2000 mg/kg, OECD 420, EU Method B.1, Pooles 2007
DERMAL: LD50 = > 2000 mg/kg, OECD 402, EU Method B.3, EPA OPPTS 870.1200,  Acute Oral Toxicity
In the key study, the acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight. 
The method was designed to meet the requirements of the standardised guidelines OECD 420 and EU Method B.1 bis.
In the supporting study, the acute oral toxicity of the test material was investigated during a procedure in which CFY strain rats were treated with the test material administered as a suspension in 0.5 % gum tragacanth. Animals were observed for a period of 14 days following dosing for signs of toxicity. All rats were autopsied and examined microscopically. Under the conditions of the study, the LD50 of the test material was estimated to be greater than 16 g/kg bw. 
Acute Dermal Toxicity
In the key study, the dermal LD50 value of the test material in Wistar rats was established to exceed 2000 mg/kg body weight.
The animals were exposed to a single limit dose of the test material at 2000 mg/kg bw. 
The method was designed to meet the requirements of the standardised guidelines OECD 402, EU Method B.3, EPA OPPTS 870.1200 and JMAFF, 12 Nohsan, Notification No. 8147, Stitzinger 2012

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 July 2007 - 30 July 2007

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8 – 12 weeks
- Weight at study initiation: The bodyweight variation did not exceed ± 20 % of the initial mean bodyweight of any previously dosed animal(s)
- Fasting period before study: overnight fast immediately before dosing and for approximately three to four hours after dosing
- Housing: The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): ad libitum. Free access to food (Certified Rat and Mouse Diet) was allowed throughout the study
- Water (e.g. ad libitum): ad libitum mains drinking water
The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
- Acclimation period: at least five days
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 – 25 °C
- Humidity (%): 30 – 70 % relative
- Air changes (per hr): at least 15 per hour
- Photoperiod (hrs dark / hrs light): the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

Experimental Preparation
For the purpose of the study the test material was freshly prepared, as required, as a suspension in arachis oil BP. Arachis oil BP was used because the test material did not dissolve/suspend in distilled water.

Doses:

A single dose of 2000 mg/kg (dose volume 10 mL/kg)

No. of animals per sex per dose:

A total of 5 female animals were dosed at 2000 mg/kg with a dose volume of 10 mL/kg

Control animals:

no

Details on study design:

Procedure
Using available information on the toxicity of the test material, 2000 mg/kg was chosen as the starting dose.

Dose Level Concentration Dose Volume Number of Rats
(mg/kg) (mg/mL) (mL/kg) Female
2000 200 10 1
In the absence of toxicity at a dose level of 2000 mg/kg, an additional group of animals was treated as follows:

Dose Level Concentration Dose Volume Number of Rats
(mg/kg) (mg/mL) (mL/kg) Female
2000 200 10 4

A total of five animals were therefore treated at a dose level of 2000 mg/kg in the study.

All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.

Clinical observations were made 0.5, 1, 2, and 4 hours after dosing and subsequently once daily for fourteen days. Morbidity and mortality checks were made twice daily.

Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.

At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Evaluation of data included identification of the number of animals that died during the study (or that were killed for humane reasons), and determination of the nature, severity, onset and duration of the toxic effects. If possible, the signs of evident toxicity were described. Evident toxicity refers to the toxic effects of sufficient severity that administration of the next higher dose level could result in development of severe signs of toxicity and probable mortality. Effects on bodyweights and abnormalities noted at necropsy were also identified

Preliminary study:

A single animal, dosed at 2000 mg/kg, did not show overt signs of toxicity following a single exposure to the test material. An additional group of animals was subsequently dosed at the same level.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths

Clinical signs:

other: No signs of systemic toxicity were noted

Gross pathology:

No abnormalities were noted at necropsy

Table 1: Individual Bodyweights and Bodyweight Changes

Dose level	Animal number and sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
2000	1-0 F	220	243	262	23	19
	2-0 F	215	237	259	22	22
	2-1 F	239	267	283	28	16
	2-2 F	243	271	291	28	20
	2-3 F	220	241	280	21	39

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the test, the LD50 of the test material was estimated to be greater than 2000 mg/kg bw.

Executive summary:

The acute oral median lethal dose (LD50) of the test material in female Sprague-Dawley rats was estimated to be greater than 2000 mg/kg bodyweight.

The method was designed to meet the requirements of the OECD Guidelines for Testing of Chemicals No 420 "Acute Oral Toxicity - Fixed Dose Method" (adopted 17 December 2001) and Method B1 bis Acute Toxicity (Oral) of Commission Directive 2004/73/EC.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study was conducted under GLP to the standardised guidelines OECD 420 and EU Method B.1 bis (awarded a reliability score of 1).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

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

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

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)

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study was conducted under GLP to the standardised guidelines OECD 402, EU Method B.3, EPA OPPTS 870.1200 and JMAFF, 12 Nohsan, Notification No. 8147.
In accordance with the criteria of Klimisch (1997) it was awarded a reliability score of 1.

Additional information

Acute Oral Toxicity

The acute oral median lethal dose (LD50) of the test material in female rats was estimated to be greater than 2000 mg/kg bodyweight. The method was designed to meet the requirements of the standardised guidelines OECD 420 and EU Method B.1.

Acute Inhalation Toxicity

In accordance with Column 2 of REACH Annex VIII, the acute inhalation study (as required under Section 8.5.2) is not considered scientifically justified on the grounds that inhalation exposure is unlikely to occur. Oral and dermal exposure routes are considered adequate to address the acute toxicity of the substance.

Acute Dermal Toxicity

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

The animals were exposed to a single limit dose of the test material at 2000 mg/kg bw.

The method was designed to meet the requirements of the standardised guidelines OECD 402, EU Method B.3, EPA OPPTS 870.1200 and JMAFF, 12 Nohsan, Notification No. 8147.

Justification for selection of acute toxicity – oral endpoint
The key study was conducted under GLP to the standardised guidelines OECD 420 "Acute Oral Toxicity - Fixed Dose Method" and EU Method B.1
In accordance with the criteria of Klimisch (1997) it was awarded a reliability score of 1.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

Acute Oral Toxicity

In accordance with the criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for acute oral toxicity.

 

Acute Dermal Toxicity

In accordance with the criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for acute dermal toxicity.