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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Scientific Opinion on the re-evaluation of propyl gallate (E 310) as a food additive
Author:
European Food Safety Authority (EFSA)
Year:
2014
Bibliographic source:
EFSA Journal 12(4), 3642
Reference Type:
publication
Title:
Final Report on the Amended Safety Assessment of Propyl Gallate
Author:
Cosmetic Ingredient Review (CIR) Expert Panel
Year:
2007
Bibliographic source:
International Journal of Toxicology 26 (Suppl. 3), 89–118
Reference Type:
publication
Title:
Fetal resorption in the rat as influenced by certain antioxidants
Author:
Telford I.R. et al.
Year:
1962
Bibliographic source:
American Journal of Anatomy
Reference Type:
publication
Title:
Effects of Dietary Administration of Propyl Gallate during Pregnancy on the Prenatal and Postnatal Developments of Rats
Author:
Tanaka S. et al.
Year:
1979
Bibliographic source:
J. Food Hyg. Soc. Vol. 20, No. 5

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Any other information on results incl. tables

Several studies on developmental toxicity of Propyl gallate has been cited in the EFSA report.

Propyl gallate was tested in a prenatal developmental toxicity study in mice given orally 3-300 mg Propyl gallate /kg/bw on gestation days (GD) 6-15 (22-25 animals/group) (FDRL, 1972, as reported in CIR, 2007). Dams were killed and fetuses removed on GD 17. Propyl gallate up to 300 mg/kg bw for 10 consecutive days had no effect on implantation or on maternal or fetal survival (CIR, 2007). The number of visceral, skeletal and external abnormalities in the test group fetuses did not differ to control animals (fed corn oil) (FDRL, 1972, as reported in CIR, 2007).

In Walter Reed-Carworth Farms rats (9 animals; average body weight 200 g) fed Propyl gallate at a dose of 0.5 g in diet (possibly equivalent to 100 mg/kg bw/day) during pregnancy, increased fetal resorption rates were observed (Telford et al., 1962, as reported in BIBRA, 1989a, CIR, 2007). In this study only one dose was tested and the number of animals per group was low. This study was therefore considered as a very limited study.

 

Propyl gallate was tested in a prenatal developmental toxicity study in rats given orally 3-300 mg Propyl gallate /kg/bw on gestation days (GD) 6-15 (22-25 animals/group). Dams were killed and fetuses removed on GD 20. Propyl gallate up to 300 mg/kg bw for 10 consecutive days had no effect on implantation or on maternal or fetal survival. The number of visceral, skeletal and external abnormalities in the test group fetuses did not differ to control animals (fed corn oil) (FDRL, 1972, as reported in CIR, 2007).

 

Female Wistar rats (20 animals/group, except 18 animals/highest dose-group) were given Propyl gallate in the diet at doses of 0, 0.4, 1 and 2.5 % (approximately equivalent to 0, 350, 880 and 2000 mg/kg bw/day) throughout pregnancy (Tanaka et al., 1979, BIBRA, 1989a). On GD 20, at least 13 dams per group were sacrificed for fetal examination (Tanaka et al.,1979); the remaining animals were allowed to deliver their litters which were autopsied at week 8 of age. The highest dose (2000 mg/kg bw/day) caused a decrease in the total number of offspring and induced a slight retardation in fetal development; a marked suppression of maternal body weight gain and food consumption was also noted (Tanaka et al., 1979). There was no evidence of increases in fetal deaths or malformations due to Propyl gallate at any concentration. Also, there was no evidence of developmental toxicity for the groups which received 350 or 880 mg/kg bw/day. Five females per group were allowed to deliver normally and appearance, behaviour and organ weights were normal in the dams and offspring (Tanaka et al., 1979 as reported in BIBRA, 1989a).

No increase in fetal abnormalities or evidence of embryotoxicity were observed in rabbits (20-50/group) given daily doses of up to 250 mg Propyl gallate /kg bw by stomach tube on GD days 6-18 (FDRL, 1973 as reported in BIBRA, 1989a, CIR, 2007).

Propyl gallate was tested in a prenatal developmental toxicity study in hamsters given orally 2.5-250 mg Propyl gallate /kg/bw on gestation GD 6-10 (22-25 animals/group) (FDRL, 1972, as reported in CIR, 2007). Dams were killed and fetuses removed on GD 14. Propyl gallate up to 250 mg/kg bw for 5 consecutive days had no effect on implantation or on maternal or fetal survival (CIR, 2007). The number of visceral, skeletal and external abnormalities in the test group fetuses did not differ to control animals (fed corn oil) (FDRL, 1972, as reported in CIR, 2007).

 

The Panel considered that the reproduction studies were not appropriate for hazard characterisation since they are old, poorly described and lack information about reproductive performance.

Data for developmental toxicity were less limited. Oral studies in mice, rats, rabbits and hamsters were available. Doses around 300 mg/kg bw/day did not appear to be associated with adverse effects and could be regarded as a NOAEL for developmental toxicity.

Applicant's summary and conclusion

Conclusions:
Based on the assessment of available data in a weight-of-evidence approach EFSA concluded, that doses around 300 mg/kg bw/day did not appear to be associated with adverse effects and could be regarded as NOAEL for developmental toxicity.
Executive summary:

In the EFSA publication "Scientific Opinion on the re-evaluation of propyl gallate (E310) as a food additive", 2014 several developmental toxicity studies conducted with Propyl gallate were presented. For mice, the study from Food and Drugs Research Labs (FDRL) (also cited in CIR, 2007) was summarized. In this prenatal developmental toxicity study mice were given 3 -300 mg/kg bw/day on gestation days (GD) 6 -15 (22 -25 animals/group). The dams were killed and fetuses were removed on GD17. Doses of up to 300 mg/kg bw given for 10 consecutive days had no effect on implantation or on maternal or fetal survival. The number of visceral, skeletal and external abnormalities in the test item treated fetuses did not differ to the control animals receiving corn oil.

For rats, the EFSA report cited and summarized data from several studies. In the study by Telford et al., 1962 Walter Reed-Carworth rats (9 animals) with an average body weight of 200 g were given Propyl gallate at a dose of 0.5 g via the diet (possibly equivalent to 100 mg/kg bw/day) during pregnancy. Increased fetal resorption rates were observed. As in this study only one dose was tested and the animal number was low the study was considered as a very limited study.

Similar to mice, FDRL also conducted a prenatal developmental toxicity study in rats given orally 3 -300 mg/kg bw on gestation days 6 -15 (22 -25 animals/group). Dams were killed and fetuses removed on GD 20. Propyl gallate up to 300 mg/kg bw for 10 consecutive days had no effect on implantation or on maternal or fetal survival. The number of visceral, skeletal and external abnormalities in the test group fetuses did not differ to control animals.

In the study by Tanaka et al., 1979 (see study specific IUCLID entry in section 7.8.2) female Wistar rats (20 animals/group, except 18 animals/high dose group) were given Propyl gallate in the diet at doses of 0, 0.4, 1 and 2.5% (approximately equivalent to 0, 350, 880 and 2000 mg/kg bw/day) throughout pregnancy. On GD 20, at least 13 dams per group were sacrificed for fetal examination. The remaining animals were allowed to deliver their litters which were autopsied at week of age. The high dose caused a decrease in total number of offspring’s and induced a slight retardation in fetal development, a marked suppression of maternal body weight gain and food consumption was also noted. There were no evidence of increases in fetal deaths or malformations due to Propyl gallate at any concentration. Also there was no evidence of developmental toxicity for the groups received 350 or 880 mg/kg bw/day. Five females per group were allowed to deliver normally and appearance, behaviour and organ weights were normal in the dams and offspring.

For rabbits, the study from FDRL, 1973 (also cited in CIR, 2007) was presented. No increase in fetal abnormalities or evidence of embryotoxicity were in observed in rabbits (20 -50/group). The animals received daily doses of up to 250 mg/kg bw by stomach tube on GD days 6 -18.

For hamsters, the study from FDRL, 1972 (also cited in CIR, 2007) was summarized. Propyl gallate was tested in a prenatal developmental toxicity study in hamsters given orally 2.5 -250 mg/kg bw on GD 6 -10 (22 -25 animals/group). Dams were killed and fetuses removed on GD14. The treatment with the test item had no effect on implantation or on maternal or fetal survival. The number of visceral, skeletal and external abnormalities in the test group fetuses did not differ to control animals fed with corn oil.

EFSA concluded, that doses around 300 mg/kg bw/day did not appear to be associated with adverse effects and could be regarded as NOAEL for developmental toxicity.