2-Propenoic acid, 2-propylheptyl ester

Endpoint summary

Description of key information

2-propylheptyl acrylate is practically nontoxic after a single ingestion. The structural analogue 2-ethylhexyl acrylate is virtually nontoxic after a single skin contact. The inhalation of a highly saturated vapour-air-mixture of 2-ethylhexyl acrylate (read across substance) represents an unlikely acute hazard. 
Oral: LD50 rat  > 2000 mg/kg bw (OECD TG 423, Austrian Research Centre, 2008)
Dermal: LD50 rabbit: ca. 7522 mg/kg bw (read across to CAS No 103-11-7; Mellon Institute for Industrial Research, 1950 )
Inhalative: LC0 rat = 1.19 mg/L (nominal, saturated vapour, 8 h) ( read across to CAS No 103-11-7; OECD403, BASF AG 1958)

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:

2008-02-18 to 2008-04-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study according to OECD TG No. 423 and in compliance with GLP regulations.

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

December 17, 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Crl:(WI)BR rats from Charles River Deutschland GmbH, D-97633 Sulzfeld.
- Age at study initiation: Approximately 8 weeks at the time of the test substance administration.
- Fasting period before study: The feed was withdrawn the evening before the administration of the test substance and was offered again about three hours afterwards.
- Housing: Single caging in Makrolon cages type III (39 cm x 23 cm bottom area, 18 cm height). Wire mesh lids. Sanitation of cages once a week.
- Diet: Ssniff R/M-H maintenance diet for rats and mice (item V1534-3 ) ad libitum, supplied by Ssniff Spezialdiaeten GmbH, 59494 Soest, Germany.
- Water: Tap water from an automatic watering system, ad libitum.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature: Average of 22.5 °C (continuous control and recording).
- Humidity: Average of 49.39 % (continuous control and recording).
- Air changes: 12 per hour.
- Photoperiod (hrs dark / hrs light): Artificial light from 6 a.m. to 6 p.m.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Justification for choice of no vehicle: The administration of the undiluted test substance was requested by the sponsor.

CLASS METHOD
- Rationale for the selection of the starting dose: As requested by the sponsor, a starting dose of 2000 mg of the test substance per kg body weight was chosen

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

Step 1: 3 females
Step 2: 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed 0.5, 1, 2, 3, 4 and 6 hours after administration (p.a.) of the test substance and then at least once a day for a total of 2 weeks. Body weights were determined before administration, 7 days p.a., and 14 days p.a.
- Necropsy of survivors performed: yes
- Other examinations performed: Observations included but were not limited to changes in skin, fur, eyes, the occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions.

Statistics:

none

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality occured, no abnormal findings were observed during the study or at necropsy

Mortality:

No mortality occured.

Clinical signs:

No abnormalities were observed.

Body weight:

All animals gained weight in both weeks p.a..

Gross pathology:

After necropsy, no abnormalities were observed.

Body weights of animals before and after administration of dose:

Animal Number  Body weight before administration  7 days p.a.  14 days p.a.   21 185  220  238   22 186  237  259   23 187  213  227   24 197  241  265   25 190  230  242   26 191  233  241

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1958-11-07

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (no analytical monitoring of test atmosphere concentration). Read across was performed with 2-ethylhexyl acrylate. Please refer to IUCLID section 13 for read across justification.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

(adopted 1981)

Deviations:

yes

Remarks:

no analytical monitoring of the test atmosphere concentration

Principles of method if other than guideline:

BASF Test
This test (also called inhalation hazard test) was performed in principle as described in OECD Guideline 403. It demonstrates the toxicity of an atmosphere saturated with vapors of the volatile components of a test substance at the temperature chosen for vapor generation (20 °C and 1002.6 hPa).
Several groups of 3 rats per sex were exposed sequentially to the vapors, generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder containing approximately 120 mL test substance for 8 hours. Compressed air without further filtering was used in order to generate the test substance atmosphere. No analytical determination of the atmosphere concentrations was performed. The nominal concentration was calculated as quotient of the amount of test substance weight loss during the exposure, which was given in the raw data, and the amount of air used during the exposure. Group-wise documentation of clinical signs was performed over the 14-day study period. Body weight of groups was determined before the start of the study and at the end of the observation period in the surviving animals. The clinical signs and findings were reported in summarized form. The study allows for an estimate of the length of time required to cause severe toxic effects resulting from exposure to an atmosphere saturated with volatile components of the test substance.

GLP compliance:

no

Test type:

other: Inhalation hazard test

Limit test:

yes

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 884 g (mean)

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

8 h

Concentrations:

1.19 mg/L

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

The vapour saturation was calculated based on the vapour pressure at 25 °C and the molecular weight.
Vapour saturation = 1.82 mg/L at 25 °C.
The assumed vapour saturation at the test temperature of 20 °C would be slightly lower than the calculated value but still greater than 1 mg/L. Thus, it can be safely concluded that the animals in the present study were indeed exposed to test substance vapours and no aerosol.

Sex:

male/female

Dose descriptor:

LC0

Effect level:

1.19 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

8 h

Remarks on result:

other: No mortality observed at a satuated atmosphere with volatile parts of the component

Mortality:

No mortality was observed when 6 rats were exposed for 8 hours to an atmosphere that had been saturated at 20°C with the volatile parts of the compound.

Clinical signs:

other: No clinical signs were noted during the test.

Body weight:

Body weights increased continuously.

Gross pathology:

Since the test animals showed neither clinical signs nor other abnormalities, the necropsy was omitted.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1950-04-20 to 1950-06-15

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report. Read across was performed with 2-ethylhexyl acrylate. Please refer to IUCLID section 13 for read across justification.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Range-finding toxicity test basically according to the method described by Smyth Jr. and Carpenter (1948).

Smyth HF Jr. and Carpenter CP (1948). J. Ind. Hyg. Toxicol. 30: 63-68

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data available.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Type of wrap: impervious "Vinylite" sheeting


REMOVAL OF TEST SUBSTANCE
- Washing: yes
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied: 5.0 and 10.0 mL/kg bw, respectively

Duration of exposure:

24 h

Doses:

5.0 and 10.0 mL/kg bw (corresponding to 4435 and 8870 mg/kg bw)

No. of animals per sex per dose:

8

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Test conditions and method according to Smyth HF Jr. and Carpenter CP (1948):
Penetration of rabbit skin was estimated by a technique closely akin to the one-day cuff method of Draize et al. (1944) using groups of at least 6 rabbits. The fur was removed from the entire trunk by clipping, and the dose was retained beneath an impervious plastic film. Dosages greater than 20 mL/kg bw could not be retained in contact with the skin. The animals were immobilized during the 24-hour contact period, after which the film was removed and the rabbits were caged for the subsequent 14-day observation period. In this study, 8 rabbits were dosed by introduction of the undiluted test substance under impervious "Vinylite" sheeting which covered their clipped trunks. The LD50 value was determined by Thompson's method.

Statistics:

The LD50 value was determined by Thompson's method.

Sex:

not specified

Dose descriptor:

LD50

Effect level:

7 522 mg/kg bw

Based on:

test mat.

Mortality:

Original value: LD50 = 8.480 mL/kg
Based on a densitiy of 0.887 g/mL, LD50 = 7522 mg/kg bw.
3 of 4 rats died at 10 ml/kg and none at 5 ml/kg
3/4 animals succumbed to a dosage of 10 mL/kg bw (= 8870 mg/kg bw), and 4/4 survived 5.0 mL/kg bw (= 4435 mg/kg bw). The estimated LD50 calculated by Thompson's method after assuming 100 % mortality at 20 mL/kg and 100 % survival at 2.52 mL/kg bw was 8.48 mL/kg bw.

Clinical signs:

no data

Body weight:

no data

Gross pathology:

no data

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

7 522 mg/kg bw

Additional information

Oral exposure route:

In the key study conducted by BASF SE (2008) two groups of 3 female Wistar rats were successively administered a dose of 2000 mg/kg bw and were observed for 14 days for lethality and clinical signs of intoxication. No mortalities occurred at the dose of 2000 mg/kg bw. Thus, based on the specifications of OECD TG No. 423 the LD50 was estimated to be > 2000 mg/kg bw. Neither clinical symptoms nor abnormalities after necropsy have been observed. Based on these test results (LD50 > 2000 mg/kg bw), 2-propylheptyl acrylate is assessed to be practically nontoxic after a single ingestion. No classification and labelling according to Annex VI of Directive 67/548/EEC and according to REGULATION (EC) No 1272/2008 is proposed.

 

Dermal exposure route:

In a study performed with the structural analogue 2-Ethylhexyl acrylate 8 rabbits/sex/dose were exposed (occlusive) to 4435 and 8870 mg/kg bw 2-ethyl hexyl acrylate for 24 h. 4/4 animals survived after given the low dose of 4435 mg/kg bw, while 3/4 animals died after given 8870 mg/kg bw 2-ethyl hexyl acrylate (Union Carbide Corporation, 1950). The estimated LD50 was 7522 mg/kg bw. In a supporting study (report from a publication of Carpenter et al., 1974), 4 white male rabbits/sex/dose were exposed (occlusive) to 2-ethyl hexyl acrylate for 24 h. The estimated LD50 was 14192 mg/kg bw. No further information was given in both studies regarding clinical signs, body weight, and necropsy findings. The substance is considered to be nontoxic after a single skin contact.

 

Inhalation exposure route:

In the key study (BASF AG, 1958) an Inhalation hazard test was performed in rats. Three male and three female rats were exposed (whole-body) to the structural analogue 2-Ethylhexyl acrylate vapours (20°C) at a nominal concentration of 1.19 mg/L (no analytical monitoring of the test atmosphere concentration but saturated atmosphere) for 8 hours. No mortality was observed, thus deducing an LC0 of 1.19 mg/L air. No clinical signs or other abnormalities were observed. No necropsy was performed. Based on the LC0 and the absence of clinical signs, indicating a possible effect on the respiratory tract, the inhalation of a highly saturated vapour-air mixture represents an unlikely acute hazard.

Justification for selection of acute toxicity – oral endpoint
GLP and guideline compliant study

Justification for selection of acute toxicity – inhalation endpoint
GLP and guideline compliant study with acceptable deviations

Justification for classification or non-classification

Based on the results of the acute toxicity studies, the test substance does not need to be classified and labelled according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP).