Propanoic acid, 2-hydroxy-, ammonium salt (1:1), (2S)-

Endpoint summary

Description of key information

The target substance did not cause any skin and/or eye effects in an acute dermal and an acute eye irritation study, which were conducted in accordance with OECD test guideline 404 and 405, respectively.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-07-25 to 2003-10-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): Ammonium-S-Lactate
- Physical state: clear colourless liquid
- Analytical purity: ca. 70 %
- Composition of test material, percentage of components: ca. 70 % ammonium lactate, ca. 30 % water
- Lot/batch No.: 2991200039
- Expiration date of the lot/batch: 2005-02-10
- Stability under test conditions: stable
- Storage condition of test material: at room temperature in the dark

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: at least 6 weeks
- Weight at study initiation: at least 1.0 kg
- Housing: individually in labelled cages with perforated floors
- Diet: standard laboratory rabbit diet approx. 100 g per day; in addition, pressed hay was provided twice a week, ad libitum
- Water: tap-water (quarterly analysis of quality available at test site), ad libitum
- Acclimation period: at least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.1-23.9 °C
- Humidity (%): 44-81 %; according to the test laboratory cleaning procedures in the room might have caused the temporary fluctuations above the optimal level of 70 % for relative humidity. Based on laboratory historical data these conditions were considered not to have affected the study integrity.
- Air changes (per hr): 15 per hour
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): 70 %

Duration of treatment / exposure:

4 h

Observation period:

1, 24, 48 and 72 h

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: 2 × 3 cm (6 cm²)
- Type of wrap if used: the test substance was applied to the skin of one flank, using a metalline patch (2 x 3 cm); the patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the dressing was removed and the skin was cleaned of residual test substance using water
- Time after start of exposure: 4 hours

SCORING SYSTEM:
The irritation was assessed according to the following numerical scoring system. At each observation, the highest scores given were recorded:

Erythema and eschar formation:
No erythema .......................................................................................................................... 0
Very slight erythema (barely perceptible) .............................................................................1
Well-defined erythema ......................................................................................................... 2
Moderate to severe erythema ............................................................................................. 3
Severe erythema (beet redness)* ....................................................................................... 4
* Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the maximum grade for erythema(= 4) is given.

Oedema formation:
No oedema ............................................................................................................................................. 0
Very slight oedema (barely perceptible) ........................................................................................... 1
Slight oedema (edges of area well-defined by definite raising) .................................................... 2
Moderate oedema (raised approximately 1 millimeter) .................................................................. 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure) 4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible within:

Remarks:

24 h

Remarks on result:

probability of weak irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Irritation (please refer to Table 1 in box " Any other information on results incl. tables"):
Four hours exposure to 0.5 mL of the test item resulted in very slight erythema in the treated skin-area of one rabbit, which had resolved within 24 hours.

Corrosion:
There was no evidence of a corrosive effect on the skin.

Other effects:

Colouration:
No staining of the treated skin by the test substance was observed.

Toxicity/mortality:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Table 1: Individual skin irritation scores

Animal #	513 (sentinel)			537			538
Time after exposure	Erythema	Oedema	comments	Erythema	Oedema	comments	Erythema	Oedema	comments
1 hour	1	0	-	0	0	-	0	0	-
24 hours	0	0	-	0	0	-	0	0	-
48 hours	0	0	-	0	0	-	0	0	-
72 hours	0	0	-	0	0	-	0	0	-

 

 Table 2: Mean value irritation scores

Animal #	Mean 24 - 72 hrs
	Erythema	Oedema
513	0	0
537	0	0
538	0	0

 

Table 3: Animal specifications

Animal #	Sex	Age at start (weeks)	Body weights (g)
			prior to application	at termination
513	M	8-10	1883	1998
537	M	7-9	1407	1509
538	M	7-9	1481	1601

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute dermal irritation/corrosion study conducted according to OECD 404, the test item was found to be non-irritating.

Executive summary:

In a primary dermal irritation study (OECD guideline 404), three male New Zealand white rabbits were dermally exposed to 0.5 mL of the test item (70% solution) for 4 hours to a body surface area of 6 cm² under semi-occlusive conditions. Animals then were observed for 1, 24, 48 and 72 hours after removal of the dressings and test substance. The test item did not cause any skin effects, except a very slight erythema in the treated skin-area of one rabbit, which had resolved within 24 hours. Based on the results, the test item is considered to be non-irritating.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005-04-06 to 2005-06-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 24th April 2002

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): Ammonium Lactate, PURASAL® NH
- Physical state: yellowish-white liquid
- pH: 5
- Analytical purity: not reported
- Impurities (identity and concentrations): not reported
- Composition of test material, percentage of components: not reported
- Isomers composition: not reported
- Lot/batch No.: 0503002615
- Expiration date of the lot/batch: 2007-09-28
- Stability under test conditions: not reported
- Storage condition of test material: room temperature (20 ± 5 °C) in the dark

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Granja Cunicola San Bernardo, S.L., Tulebras, Navarra, Spain
- Age at study initiation: 14-15 weeks
- Weight at study initiation: 3.1-3.5 kg
- Housing: individually in stainless steel cages (52 × 58 × 43 cm) with a grille floor and placed on a rack
- Diet: free access to a standard diet
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 40-70
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated left eye was used as a control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): undiluted, 100%

Duration of treatment / exposure:

24 h

Observation period (in vivo):

14 days

Number of animals or in vitro replicates:

3

Details on study design:

ADMINISTRATION OF THE TEST ITEM
Both eyes of the animals were examined before treatment in order to reject them if they showed any signs of eye alterations. One single application of the test item was done.The administration was carried out with the animal immobilised and the test item was dropped into the right conjunctival sac, made perfectly accessible by carefully pulling the lower lid outwards. Once the test item had been administered, the lids of the treated eye were held
together for one second. Immediately after administration, the rabbits were fitted with a plastic collar for 1 hour to prevent them from rubbing their eyes.

OBSERVATIONS
The behaviour of the animals was observed immediately following instillation of the product and they were then returned to their cages and observed at regular intervals so as not to miss any serious effect of the test item. The degree of ocular irritation was assessed after approximately 1 hour, and approximately 24, 48, 72 hours, 7 and 14 days after the treatment, following the criteria described below. For the direct examination, the assessments were carried out in the following order: conjunctivae (edema, redness, lacrimation), iris and cornea (degree and extent of opacity). Subsequently, and at all the observations except the one at one hour after administration, the observation of the cornea was completed with the instillation of an aqueous solution of 2 % sodium fluorescein (Colircusi Fluoresceina®, Laboratorios Cusi, S.A., Batch 4CRK1A). This procedure involved the instillation of the aqueous solution of fluorescein in the test area, followed by washing the area with a 0.9 % physiological saline solution. Once the excess fluorescein had been removed, the corneal alterations were observed with the aid of a transilluminator with a cobalt blue filter

SCORING SYSTEM: According to OECD guideline 405

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 27 h

Remarks on result:

probability of weak irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

probability of weak irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of mild irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.4

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.4

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

probability of weak irritation

Irritant / corrosive response data:

The test item was administered initially to one animal (no. 1997). One and 24 hours after the application, some blood vessels hyperaemic (injected) (grade 1) and some swelling above normal (grade 1) was recorded, accompanied by slight lacrimation in the case of the observation carried out 24 hours after the administration. Forty-eight hours after the administration, some hyperaemic blood vessels (injected) (grade 1) were still observed in this animal, but the edema had remitted completely. No ocular lesions were recorded in this animal 72 hours, 7 or 14 days after the administration.
The test item was afterwards applied to two more animals (nos. 2011 and 2012). One hour after the administration, one of these animals (no. 2011) was seen to have redness diffuse, crimson colour, individual vessels not easily discernible (grade 2) accompanied by obvious swelling, with partial eversion of the lids (grade 2). Twentyfour hours afterwards, diffuse redness, crimson colour, and individual vessels not easily discernible (grade 2), were still observed, but the edema had diminished to some swelling above normal (grade 1 ). One hour and 24 hours after the application, slight lacrimation was also observed in this animal. Forty-eight hours after the administration, some hyperaemic blood vessels (injected) (grade 1) were observed. No ocular lesions were recorded 72 hours, 7 or 14 days after the administration.
One, 24 and 48 hours after the administration, diffuse redness, crimson colour, and individual vessels not easily discernible (grade 2) were observed in the remaining animal (no. 2012). One hour after the administration, swelling, with the lids about half closed (grade 3), was also recorded in this animal. This lesion diminished progressively to obvious swelling, with partial eversion of lids (grade 2) during the observation carried out 24 hours after the application, and to some swelling above normal (grade 1) during the observation carried out 48 hours after the application. Slight lacrimation (grade 1) was also recorded in this animal one hour and 24 hours after the treatment. Seventy-two hours and 7 days after the application, some hyperaemic blood vessels (injected) (grade 1) were observed, which had remitted completely 14 days after the administration.

Other effects:

CLINICAL SIGNS AND BODY WEIGHT
The behaviour and physical state of the rabbits, and the body weight evolution were normal throughout the study.

Table 1: Body weight (kg)

		Observation period
Animal #	Day of treatment	24h	48h	72h	7d	14d
1997	3.49	3.52	3.54	3.52	3.65	3.76
2011	3.21	3.23	3.29	3.27	3.39	3.51
2012	3.06	3.04	3.09	3.08	3.18	3.29

Table 2: Primary Eye Irritation Test

Animal #	Region of eye		Observation period
			1h	24h	48h	72h	7d	14d
1997	Cornea	Density	0	0	0	0	0	0
	Iris		0	0	0	0	0	0
	Conjunctivae	Hyperaemia	1	1	1	0	0	0
		Edema	1	1	0	0	0	0
2011	Cornea	Density	0	0	0	0	0	0
	Iris		0	0	0	0	0	0
	Conjunctivae	Hyperaemia	2	2	1	0	0	0
		Edema	2	1	0	0	0	0
2012	Cornea	Density	0	0	0	0	0	0
	Iris		0	0	0	0	0	0
	Conjunctivae	Hyperaemia	2	2	2	1	1	0
		Edema	3	2	1	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute eye irritation/corrosion study conducted according to OECD 405, the test item is considered to be non-irritant.

Executive summary:

In a primary eye irritation study (OECD 405) 0.1 mL of the test item was instilled into the conjunctival sac of one eye of each of three young adult New Zealand White rabbits. Animals were observed for 14 days. Irritation was scored by the method of Draize. The behaviour and physical state of the rabbits, and the body-weight evolution were normal throughout the study. Only very mild conjunctival reactions were observed, which were fully reversible within 72 hours (two animals), and for the third animal within 14 days. Based on the results, the test item can be considered as not irritating.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Ammonium-S-lactate was tested negative for skin and eye irritating properties in studies conducted according to OECD test guidelines 404 and 405. Thus, in accordance with CLP Regulation 1272/2008 no classification for eye or skin irritation is warranted.

Justification for classification or non-classification

Ammonium-S-lactate did not cause any skin and/or eye effects in an acute dermal and in an acute eye irritating study in accordance with OECD test guideline 404 and 405. Based on these results, classification of ammonium-S-lactate is not warranted.