4-hydroxybutyl acrylate

Carcinogenicity

Description of key information

Data from structural analogue 2-hydroxyethyl acrylate (CAS No. 818-61-1):

Following chronic exposure by the inhalation route (5 d/w, 6 h/d), the NOAEC for general toxicity in Sprague-Dawley rats was 0.0024 mg/L (nominal) based on an increased incidence, increased severity, and earlier onset of the lesions associated with the chronic murine pneumonia. Gross and histopathological examination of tissues from rats exposed to concentrations of 0.024 and 0.0024 mg/L showed no indication of a carcinogenic effect.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Justification for type of information:

Please see for more information the read-across justification in Section 13.

Reason / purpose for cross-reference:

read-across source

Key result

Dose descriptor:

NOAEC

Effect level:

>= 0.024 mg/L air (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

histopathology: neoplastic

Remarks on result:

other: Result read-across CAS No. 818-61-1

Remarks:

Correction for molecular weight not required.

Key result

Critical effects observed:

no

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

24 mg/m³

Study duration:

chronic

Species:

rat

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No 1272/2008. Based on the data, classification for carcinogenicity is not warranted under Regulation (EC) No 1272/2008.

Additional information

No reliable studies concerning carcinogenicity were identified for 4-hydroxybutyl acrylate (HBA). However, data from the structural analogue 2-hydroxyethyl acrylate (HEA, CAS No. 818-61-1) are considered appropriate for the assessment.

In a chronic inhalation study (Dow Chemical Co., 1979), male and female Sprague-Dawley rats (99 or 100 animals/ sex/dose group) were exposed to atmospheres containing 0 ppm (controls), 5.0 ppm (0.024 mg/L) or 0.5 ppm (0.0024 mg/L) 2-hydroxyethyl acrylate (HEA) for 6 hours/day, 5 days/week over an 18 month period, and subsequently held for a post-exposure period of 5 months (males) and 6 months (females). The study included 12-month interim sacrifices for pathologic and cytogenetic examinations. Haematology, blood chemistry and urine analysis were measured prior to the scheduled 12-month interim sacrifice, and again after 5 months of the post-exposure observation period. Histopathological examination was carried out for the following tissues of the control and 5 ppm groups, at interim and terminal sacrifice: brain, heart, liver, kidneys, testes, lungs, thoracic and/or mesenteric lymph nodes, salivary glands, pancreas, adrenals, spleen, thymus, aorta, skeletal muscle, small intestine, large intestine, thyroid gland, trachea, spinal cord, peripheral nerve, pituitary gland, epididymides, urinary bladder, accessory sex glands, adipose tissue, ovaries, uterus, nasal turbinates, and any gross lesion suggestive of a pathologic process or with tumor formation. At 0.5 ppm terminal sacrifice the following tissues were examined by light microscopy: lungs, liver, kidneys, lymph nodes, tracheas and all grossly visible lesions from all surviving animals; at interim sacrifice all grossly visible lesions or tissues where lesions had been seen at 5 ppm. Rats dying or culled during the course of the study, were subjected to complete necropsy and microscopic exam as described above (except when autolysis precluded evaluation) and the presence and absence of neoplasms was recorded. Body weights, terminal organ weights and cumulative mortality, urinalysis, clinical chemistry and haematology did not appear to be altered by chronic HEA exposure. Overall treatment was not associated with adverse effects except that the rats in the 5 ppm treatment group developed yellow staining of the fur and a marginal increase in Mycoplasma-induced chronic murine pneumonia which was interpreted as being treatment-related. No treatment-related effects were seen in the 0.5 ppm group. A variety of neoplasms considered spontaneous in origin occurred in a number of tissues or organs of control and exposed groups of rats. As expected, mammary fibroadenomas and pituitary adenomas were the most frequently occurring neoplasms in female rats of all groups. Adrenal pheochromocytomas, pancreatic acinar adenomoas, pituitary adenomas and subcutaneous fibromas were the most common neoplasms in the male rats of all groups. Neoplasms, all of which were considered spontaneous in origin, occurred in the following organs and tissues: liver, lung, pancreas, kidney, testes, preputial gland, stomach, small and large intestine, spinal cord and peripheral nerves, pituitary gland, subcutaneous tissue, mammary tissue, integument, ear canal, oral cavity, adrenal gland, lymph nodes, spleen, brain, adipose tissue, thyroid, ovary, uterus, clitoral gland and vagina. Statistical analyses revealed no exposure-related increases in the incidence of any of these neoplasms in HEA exposed rats compared to control rats. Statistical analyses also revealed no differences between the temporal or total incidence of HEA-exposed rats bearing benign neoplasms, malignant neoplasms, or all types of neoplasms combined compared to control rats. Overall chronic inhalation exposure to HEA at a dose of 5 ppm caused only a minimal toxicological effect while no toxicity was seen at 0.5 ppm. Gross and histopathological examination of tissues showed no indication of significant chronic toxicity or a carcinogenic effect in either the 5 or 0.5 ppm treatment groups.

The NOAEC for general toxicity was set at 0.0024 mg/L (nominal) based on an increased incidence, increased severity, and earlier onset of the lesions associated with the chronic murine pneumonia observed at the high dose level. The NOAEC for carcinogenicity was equal to or greater than the highest dose tested (0.024 mg/L, nominal).