Acrylic acid

Endpoint summary

Description of key information

Acrylic acid is of moderate toxicity after a single ingestion and after short-term inhalation exposure. Acrylic acid is not toxic after short-term skin contact, when tested in non-corrosive concentrations.

Oral: LD50 = between 1000 and 2000 mg/kg b.w. (male rats)

Dermal: LD50 > 2000 mg/kg bw (rabbit, occlusive)

Inhalation: LC50 > 5.1 mg/L (rat, vapour saturated atmosphere)

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:

2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Lot No. A829F1C020
- Expiration date of the lot/batch: Jan 12, 2016
- Purity: 99.73 %
- Physical description: colourless clear, pungent liquid

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test substance was administered as a 20 %, 5 % or 2.5 % w/w mixture in distilled water.

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories, Inc. on February 11, March 4, and April 22, 2015
- Age at study initiation: young adult, 9 - 11 weeks
- Weight at study initiation: 157 - 199 grams at experimental start
- Fasting period before study: overnight
- Housing: singly
- Diet (e.g. ad libitum): ad libitum (except during fasting), Harlan Teklad Global 16 % Protein Rodent Diet
- Water (e.g. ad libitum): ad libitum, filtered tap water
- Acclimation period: 9 - 19 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23 °C
- Humidity (%): 40 - 57 %
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: The test substance was administered as a 20 %, 5 % or 2.5 % w/w mixture in distilled water.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg administered at a 20 % w/w mixture in distilled water

Doses:

2000 mg/kg as 20 % solution in distilled water
2000 mg/kg as 5 % solution in distilled water
300 mg/kg as 5 % solution in distilled water
1000 mg/kg as 2.5 % solution in distilled water

No. of animals per sex per dose:

300 and 1000 mg/kg: 6
2000 mg/kg: 3 animals for 20 % solution and 3 animals for 5 % solution

Control animals:

no

Details on study design:

- Duration of observation period following administration: short-term outcome: 48 h, long-term outcome: 14 days
- Frequency of observations and weighing: Individual body weights were recorded prior to the test substance administration (initial) and again on Days 7 and 14 (terminal) following dosing or after death. The animals were observed for mortality, signs of gross toxicity, and behavioural changes 30 min post-dosing and at least once daily thereafter for 14 days after dosing or until death occured.
- Necropsy of survivors performed: yes
- Other examinations performed: Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

Statistics:

Statistical analysis was limited to the calculation of the mean density value for dosing.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 1 000 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Mortality was observed in all animals tested with 2000 mg/kg (as 20 % and as 5 % solution) in distilled water.
One animal died after dosing of 1000 mg/kg as 2.5 % solution in distilled water.

Clinical signs:

other: All animals of the highest dose group showed hypoactivity with irregular respiration and hunched posture. All animals of the test group with 1000 mg/kg showed hypoactivity with irregular respiration and reduced fecal volume. One animal additionally showed

Table 1: Individual Body Weights, Doses and Mortalities

Animal No.	Sex	Dose Level [mg/kg]	Body weight [g]			Dose [mL]	Mortality
			Initial	Day 7	Day 14		Day	Weight [g]
3101	M	2000	164	-	-	1.6^1	1	163
3102	M		160	-	-	1.6^1	1	157
3103	M		157	-	-	1.6^1	1	154
3104	M		170	-	-	6.8^2	0	169
3105	M		176	-	-	7.1^2	0	174
3106	M		179	-	-	7.2^2	1	168
3107	M	300	199	230	258	1.2^3	S	-
3108	M		197	224	243	1.2^3	S	-
3109	M		194	226	243	1.2^3	S	-
3110	M		197	223	246	1.2^3	S	-
3111	M		192	190	200	1.2^3	S	-
3112	M		195	229	256	1.2^2	S	-
3113	M	1000	193	217	247	7.7^4	S	-
3114	M		191	145	-	7.6^4	12	138
3115	M		191	219	243	7.6^4	S	-
3116	M		188	217	236	7.5^4	S	-
3117	M		183	193	215	7.3^4	S	-
3118	M		192	218	234	7.7^4	S	-

S: Survived to study termination (euthanized via CO₂inhalation after wighing on Day 14)

¹: The test substance was administered as a 20 % w/w mixture in distilled water. Density 1.010 g/mL

²: The test substance was administered as a 5 % w/w mixture in distilled water. Density 0.998 g/mL. Due to the high volume of the dose solution to be administered (40.08 mL/kg), each animal’s dose was divided into two approximately equal portions and administered two hours apart.

³: The test substance was administered as a 5 % w/w mixture in distilled water. Density 0.998 g/mL.

⁴: The test substance was administered as a 2.5 % w/w mixture in distilled water. Density 1.003 g/mL. Due to the high volume of the dose solution to be administered (39.88 mL/kg), each animal’s dose was divided into two approximately equal portions and administered two hours apart.

Table 2: Individual Cage Side Observations

Animal Number	Dose Level [mg/kg]	Findings	Day of Occurence
3107 - 3112	300	Active and healthy	0 – 14
3113	1000	Active and healthy Hypoactivity Irregular respiration Reduced fecal volume	0 (0.5-2.5 hrs), 4 - 14 0 (3 hrs) - 2 0 (3 hrs) - 3 1 - 3
3114		Active and healthy Hypoactivity Irregular respiration Reduced fecal volume Hunched posture Unthrifty appearance Euthanized for humane reasons	0 (0.5-2.5 hrs), 4 - 6 0 (3 hrs) – 3, 7 0 (3 hrs) – 3, 7 - 12 1 – 3 7 8 – 12 12
3115		Active and healthy Hypoactivity, irregular respiration Reduced fecal volume	0 (0.5-2.5 hrs), 4 - 14 0 (3 hrs), - 3 1
3116		Active and healthy Hypoactivity, irregular respiration Reduced fecal volume	0 (0.5 hrs), 2 - 14 0 (2.5 hrs), - 1 1
3117		Active and healthy Hypoactivity, irregular respiration Reduced fecal volume	0 (0.5 hrs), 3 - 14 0 (2.5 hrs), - 1 1 - 2
3118		Active and healthy Hypoactivity, irregular respiration Reduced fecal volume	0 (0.5-2.5 hrs), 2 - 14 0 (3 hrs), - 1 1
3101 – 3103	2000	Hypoactivity, irregular respiration Hunched posture Dead	0 (0.5-5.5 hrs) 0 (3 – 5.5 hrs) 1
3104, 3105		Active and healthy Hypoactivity, irregular respiration Hunched posture Dead	0 (0.5 hrs) 0 (1.5 – 3 hrs) 0 (2.5 – 3 hrs) 0 (5 hrs)
3106		Active and healthy Hypoactivity, irregular respiration Hunched posture Dead	0 (0.5 hrs) 0 (1.5 – 5 hrs) 0 (2.5 – 5 hrs) 1

Interpretation of results:

Category 4 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 000 mg/kg bw

Quality of whole database:

OECD TG 423

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

The test animals (10 female, 10 male rats) were exposed to atmospheres, saturated with test substance vapours for 4 hours.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): Acrylic acid, pure
- Analytical purity: > 99%

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Firma MUS RATTUS, Brunnthal.
- Weight at study initiation: 185 ± 15 g
- Housing: air-conditioned chambers
- Diet (ad libitum): Herilan MRH (Firma H. EGGERSMANN KG, Rinteln/Wesser)
- Water (ad libitum): tap water

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

- Exposure apparatus:
The exposure apparatus consisted of whole-body inhalation system. Groups of 5 animals was restrained in cages and the cages were placed into a
stainless steel and glass exposure chamber with a capacity of 200 litres.

- System of generating vapours:
The test substance was pumped into an evaporator, whose temperature was maintened at 50°C, using a continuous infusion pump (UNITA I, B. Braun). The resulting vapours were mixed with the fresh air flow and conducted into the inhalation system.

- Brief description of analytical method used:
To monitor the test substance vapour concentration in the cages, an HP Model 5840 A gas chromatograph (GC) equipped with a flame
ionization detector was used.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

4.25 and 5.12 mg/L (analytically determined)

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: prior to exposure and on postexposure days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology

Statistics:

The statistical assessment was based on the bionomial test (Wittig H.: mathematische Statistik, 1974, 32-35) performed by BASF data processing center.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.1 mg/L air (analytical)

Exp. duration:

4 h

Mortality:

No rats died during exposure or during the 14-day postexposure period.

Clinical signs:

other: Clinical signs observed on the day of exposure included reddish periocular and perinasal lacrimination, salivation, eyelid closure, scrubby clotted skin and dyspnoea. The animals of both groups were 4 and 5 days respectively after the exposure without

Body weight:

A lower body weight gain was observed (both sexes) on both postexposure Days 7 and 14 relative to the control group.

Gross pathology:

No macroscopic lesions were observed in animals sacrificed at the end of the 2-week postexposure period.

Table 1: Results

Group	Dose mg/L	Mortality Dead/Treated
		male	female
2	4.25	0/10	0/10
1	5.12	0/10	0/10

Interpretation of results:

Category 3 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

5 100 mg/m³ air

Quality of whole database:

similar to OECD TG 403

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:

08. Feb. - 22. Feb. 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: U.S. EPA Health Effects Test Guidelines, OCSPP 870.1200

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Composition: 20% acrylic acid Lot # 0104111S09
80% deionized water
Physical description: Clear colorless liquid
Solubility: Soluble in water.
Stability: Test substance was expected to be stable for the duration of testing.
Expiration Date: January 4, 2012

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Robinson Services, Inc.
- Age at study initiation: 13 weeks
- Weight at study initiation: 1937 - 2221 g (males), 1814 -2176 g (females)
- Fasting period before study:
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors, which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 2011). Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet (e.g. ad libitum): Purina Rabbit Chow #5326
- Water (e.g. ad libitum): Filtered tap water was supplied ad libitum by an automatic water dispensing system.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22°C
- Humidity (%): 22-38 %
- Air changes (per hr): 10 - 14
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

Two thousand mg/kg of body weight of a 20% aqueous dilution of the test substance in distilled water (v/v) was applied evenly over a dose area of approximately 2 inches x 3 inches (approximately 10% of the body surface) and covered with a 4-inch x 8-inch, 6-ply gauze pad. The gauze pad and entire trunk of each animal were then wrapped with 3-inch Durapore tape to avoid dislocation of the pad and to minimize loss of the test substance. The rabbits were then returned to their designated cages. The day of application was considered Day 0 of the study. After 24 hours of exposure to the test substance, the pads were removed and the test sites were gently cleansed of any residual test substance.

Duration of exposure:

24 hours

Doses:

2000 mg/kg of body weight of a 20 % aqueous dilution of th etest substance in distilled water

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for mortality, signs of gross toxicity, and behavioral changes during the
first several hours after application and at least once daily thereafter for 14 days. Observations included gross evaluation of skin and fur, eyes and mucous
membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma. Individual body weights of the animals were recorded prior to test substance application
(initial) and again on Days 7 and 14 (termination).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: Other than the dermal irritation, discoloration, fissuring and/or mechanical damage noted at the dose site of all animals throughout the 14-day observation period, there were no other clinical findings recorded for any animal over the course of the observ

Gross pathology:

No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Other findings:

none reported

Table 1: Results

Animal No.	Sex	Body weight (g)			Dose^1
		Initial	Day 7	Day 14	mL
3801	M	1955	2124	2296	19.2
3802	M	2104	2288	2404	20.7
3802	M	2221	2287	2409	21.8
3804	M	1937	2071	2142	19.0
3805	M	2008	2042	2189	19.7
3806	F	2176	2344	2513	21.4
3807	F	2007	2167	2389	19.7
3808	F	2009	2064	2218	19.7
3809	F	1814	1946	2092	17.8
3810	F	2046	2086	2286	20.1

¹The test substance was applied as a 20% v/v mixture in distilled water. Specific Gravity - .1.017 g/mL

 

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

OECD TG 402

Additional information

Oral exposure route:

A Limit Test (BASF SE, 2015) was conducted using a starting dose level of 2000 mg/kg administered at a 20 % w/w mixture in distilled water to three healthy male rats by oral gavage. Due to mortality in these animals, three additional males were dosed at the same dose level administered at a 5 % w/w mixture in distilled water. Since all of these animals died, six additional animals in two consecutive groups of three rats each were dosed at the next lowest dose level of 300 mg/kg at a 5 % w/w mixture in distilled water. At the request of the Sponsor, a dose level of 1000 mg/kg administered at 2.5 % w/w mixture in distilled water to three healthy male rats by oral gavage. Due to mortality in one animal, three additional males were dosed at the same dose level administered at a 2.5 % w/w mixture in distilled water. Since the animals survived, no additional testing was required. All animals were observed for mortality, signs of gross toxicity, and behavioural changes at least once daily for 14 days after dosing or until death occured. Body weights were recorded prior to administration (initial) and again on Days 7 and 14 (terminal) following dosing or after death. Necropsy was performed on all animals.

In an acute toxicity study conducted by BASF AG (1958) groups of 1 - 5 rats were administered doses of 20 - 5010 mg/kg bw by gavage and observed for 7 days for lethality and clinical signs of intoxication. The mortality rate was 0/1, 0/1, 0/1, 1/4, 4/5, 5/5, and 1/1 at 20, 79, 316, 1260, 2040, 3160, 5010 mg/kg bw, respectively. The LD50 was found to be approx. 1500 mg/kg bw. Clinical symptoms were unspecific: abdominal position. No necropsy was performed or documented.

 

The acute toxicity of acrylic acid to SPB (Sprague-Dawley) and CDF (Fisher 344-derived) rats by the oral route was investigated in a well-documented, GLP-compliant study by Dow Chemical (1980). Groups of 5 rats/sex/strain/dose level received the undiluted test compound by single-dose oral gavage. The following dose levels were chosen for testing in one or both strains: 31.6, 63, 126, 158, 316, 630, 1260, 1580, 2000, 2520, 5000 mg/kg bw. For reasons of animal welfare, not all dose levels were tested in both strains and both sexes. LD50 values were calculated for male and female Sprague-Dawley, and male and female CDF rats, respectively. Using Moving Average analysis, the LD50 values were determined to be 1337, 718, 151, and 526 mg/kg bw, respectively. Using Probit analysis, the respective LD50 values were 1405, 617, 146, and 468 mg/kg bw. Thus, the LD50 in Sprague-Dawley rats was 617-1405 mg/kg bw (Probit), and in CDF rats 146-468 mg/kg bw (Probit). With respect to clinical signs and the gross-pathological investigation, no detailed information was given.

 

In addition, Carpenter et al. (1974) published a LD50 of approx. 357 mg/kg bw in Wistar rats by single-dose oral gavage.

Other acute oral LD50s in rats, rabbits and mice were described mostly without additional data and ranged between 250 and 1350 mg/kg bw (BASF AG 1958, Klimkina 1969, Majka 1974).

 

Dermal exposure route:

An acute dermal toxicity test (BAMM 2011) was conducted with rabbits to provide information on the potential health hazards from short term exposure to acrylic acid at non-corrosive concentrations via the dermal route. Acid was tested as a preparation of 20% Acrylic Acid in water to produce toxicity from a single topical application. Under the conditions of this study, the single dose acute dermal LD50 of the acrylic acid is greater than 2000 mg/kg of body weight in male and female rabbits. All animals survived exposure to 2000 mg/kg acrylic acid and gained body weight during the study. Dermal irritation, discoloration, fissuring, and/or mechanical damage were noted at the dose site of all animals throughout the 14 -day observation period. There were no other findings recorded for any animal over the course of the observation period, also necropsy did not show gross abnormalities.

 

These results thus indicate that deaths observed at lower dose levels in earlier studies (described below) were likely due to the extensive local corrosivity, and not to systemic toxicity. This is furthermore supported by the absence of adverse effects in chronic dermal toxicity studies with acrylic acid.

 

Acute dermal toxicity using undiluted acrylic acid is dominated by the severe local corrosivity caused by dermal contact; dermal LD50 values of approx. 748 mg/kg bw (Carpenter et al. 1974) and approx. 640 mg/kg bw (BASF AG 1979) were demonstrated for New Zealand White and White Vienna rabbits, respectively.

 

Carpenter (1974) used 3 doses (420, 840, 1680 mg/kg bw) of undiluted acrylic acid with a 24 hour contact period under occlusive conditions (impervious sheeting). Starting with the exposure animals were immediately highly agitated and crying. Necrosis was recorded for all contact sites. After application of 420 mg/kg 1/4 animals died within 24 hours, 2 of 4 animals at 840 mg/kg and 4 of 4 animals at 1680 mg/kg, also within 24 hours.

 

In the BASF study doses of 400 and 640 mg/kg bw of undiluted acrylic acid were applied under occlusive conditions for 24 hours to the skin of 5 male and 5 female White Vienna rabbits per dose. After application of 400 mg/kg 1/5 males and 1/5 females died on day 7 or later; after application of 640 mg/kg 2/5 males and 3/5 females died within 24 hours. In addition to severe local necrosis, the treated animals showed apathy, dispnoea and poor general state. Necropsy demonstrated dilatation and acute hyperaemia of the heart and lung oedema in the deceased animals. The dilatation of the right cardiac ventricle together with an acute congestion of the heart is a common finding due to acute cardiovascular failure. In the present study, the animals revealed a massive acute skin necrosis. The massive skin necrosis led to massive pain accompanied by centralisation of blood and cardiovascular imbalance leading finally to a shock. Shock is the final common pathway for several potentially lethal clinical events, including extensive trauma. Shock is characterized by systemic hypotension due to either reduced cardiac output or reduced effective circulating blood volume. Animals, which died due to a cardiovascular failure during shock reveals also an acute congestion of heart

 

Both studies were rated with a ‘not assignable’ (Klimisch 4) reliability as the test was conducted at corrosive concentrations. Mortality observed is considered as a secondary effect arising from local severe skin damage and not from true systemic toxicity of acrylic acid.

 

The severity of corrosive effects of undiluted acrylic acid is also indicated in irritation/corrosivity studies listed under IUCLID section 7.3. The key study (BASF AG, 1998) reports full thickness destruction of skin tissue as a result of a 3 minutes exposure of rabbit skin to undiluted acrylic acid. Furthermore, tests with 2 of the animals had to be discontinued because of the severe irritation. In a second study, undiluted acrylic acid also induced full thickness destruction of skin tissue with scar formation as a result of an exposure period of even 1 minute. After application of the undiluted test substance for 5 and 15 min, respectively, anaemic necrosis followed by formation of deep scars was observed (BASF AG, 1958).

 

In conclusion, results from acute dermal toxicity testing with undiluted acrylic acid with an exposure period of 24 hours under occlusive conditions are compromised by severe corrosion, inducing inter alia pain and shock in exposed animals. Rabbits clearly showed signs of severe stress and pain (see e.g. Carpenter 1974). Thus, effects reported in these studies cannot be attributed to an intrinsic toxic property of the test substance induced by exposure via the dermal route.

 

Inhalation exposure route:

In an acute inhalation study groups of 10 Sprague-Dawley rats per sex were exposed by head-nose exposure to saturated vapour atmospheres at concentrations of 4.25 and 5.12 mg/L (analysed) for 4 hours and observed for 14 days (BASF AG 1980). No rats died during exposure or during the 14-day post-exposure period. Clinical signs of toxicity included: reddish periocular and perinasal lacrimination, salivation, eyelid closure, scrubby clotted skin and dyspnoea. The animals of both groups were 4 and 5 days respectively after the exposure without findings. No macroscopic lesions were observed in animals sacrificed at the end of the 2-week post exposure period. Thus, the 4- hour rat LC50 was > 5.1 mg/L.

 

In addition, an Inhalation Hazard Test was performed (BASF AG, 1979). Several groups of 3 Sprague-Dawley rats per sex were exposed sequentially to saturated acrylic acid vapours for different time periods (30 min, 1 and 3 hours) at 20 °C. The exposure time not causing lethality was determined. No analytical determination of the atmosphere concentrations was performed. Nominal test substance concentrations were: 21.5 mg/L (30 min and 1 h) and 22.5 mg/L (3h). Since the saturated vapour concentration of acrylic acid was estimated to be approx. 12.8 mg/L, the actual vapour concentrations of acrylic acid were either lower than the nominal concentrations, or the test substance was at least partially present as aerosol in the test atmosphere. No mortality was observed after 30 min exposure. After 1 h and 3 h 1/6 and 6/6 animals died, respectively. Clinical signs included: eyelid closure, salivation, periocular and reddish perinasal lacrimination, clotted eyes, dyspnoea, corneal opacity, diminished pain reflex, tremulous and tottered movement, nose and eye corrosion, and scrubby fur.

 

In addition, Battelle conducted a single dose inhalation toxicity study in Cynomolgus monkeys in compliance with the EPA guidelines (40 CFR Part 792) (Rohm & Haas Co., 1995). Five groups of primates, three animals each, were exposed via head-only inhalation exposure to a common target vapour concentration (75 ppm) of the test substance or filtered air (control). Each animal received a single exposure of either three or six hour duration. The achieved mean test substance vapour concentration values were all within 8 % of the target concentration and the percent relative standard deviations were all less than 10 percent. The inhaled dose was calculated for each animal based on its body weight, mean test substance concentration value and total inhaled volume. The individual animal inhaled doses for Acrylic acid ranged from 12.7 mg/kg bw (animal #401) to 35.2 mg/kg bw (animal #503). All animals survived the exposures in good condition. No clinical signs of toxicity were observed and no treatment related findings were observed during the gross pathological examination.

The acute inhalation toxicity of acrylic acid was further investigated using Sprague-Dawley rats. Two inhalation exposures were conducted in which five animals/sex were exposed once to an atmosphere of acrylic acid generated by static method or dynamically generated from liquid acrylic acid using a bubbler method for one hour and then observed for 14 days post-exposure. The LC50 determined using the static method was >4.31 mg/L (air) and under dynamic exposure conditions a LC50 of >6.74 mg/L (air) was reported (Bushy Run, 1988).

In a further study by Silver et al., 1981, groups of male rats were exposed to test substance vapours at different concentrations for 1-hour periods. Respiratory frequency was measured and the calculated decreases in respiratory frequency were used as an index of respiratory irritancy due to acrylate compounds. Tidal volume, minute ventilation and rectal temperature were also measured. In addition, the effect of pre-treatment with 125 mg/kg bw TOTP (Triorthotolyl Phosphate), a carboxylesterase inhibitor, i.p. on respiratory irritancy was investigated. Dose-dependent decreases in respiratory frequency, minute volume, tidal volume and rectal temperature occurred during inhalation of acrylic acid with minute volume being the most sensitive index. TOTP pre-treatment did not alter the respiratory irritancy caused by acrylic acid. The LC50 with and without TOTP pre-treatment was >3.9-<4.8 mg/L (air).

Exposure to a saturated acrylic acid vapour atmosphere for a period of 8 hours did not cause any mortality in the exposed rats (Smyth, 1962). Rats exposed to a saturated atmosphere of acrylic acid vapours for one hour did not result in any mortality in rats, the LC0 was ca. 6 mg/L air (Carpenter, 1974). Majka et al., 1974 exposed groups of white male Wistar rats to vapour atmospheres of the test substance for periods of 4 hrs. Exposure to 2.97 mg/L test substance vapours did not cause any mortality. The LC50 was 3.6 mg/L air. In a study that investigated the effects on respiration rates in the surgically isolated upper respiratory tracts of rats, the respiration rates in control animals exceeded 140 breaths per minute and were similar in all ester and acid exposure groups. Nasal lavage protein concentrations averaged about 300 µg/mL in control groups and were not significantly different in any acid- or ester-exposed group (Morris, 1995). Exposure of rats to dynamic atmospheres, saturated with test substance vapours did show nose and eye irritation (Gage, 1970).

Several further studies could not be used for assessment since only minor information on material and methods were available (UnionCarbide 1977, Rohm&Haas 1988, Kennedy 1991, NIOSH/RTECS 2008).

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available data for acute toxicity are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on this data, the substance is considered to be classified for acute oral toxicity Cat. 4 (H302) and acute inhalation toxicity Cat.4 (H332) under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521. The substance is harmonized classified according to Regulation (EC) No 1272/2008, Annex VI for oral toxicity Cat.4 (H302), acute dermal toxicity Cat.4 (H312) and acute inhalation toxicity Cat.4 (H332).