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Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
Reprotoxicity:
NOAEL 0.1% in drinking water for mice
Additional information

The results of the NTP two-generation reproduction study, which can be used to determine effects on fertility, is summarized in the following table.

Study reference

Study type

Results

Reliability

KEY_1985_EHRT_NTP85-322

2-generation study in mice, dose levels 0, 0.1 and 0.2% in drinking water

F1, 0.2%: reduced nr of litters per pair, reduced litter weights

F2, 0.2%: reduced nr of live pups, reduced nr of live female pups, reduced prostate weight, increased kidney weight, increased incidence abnormal sperm

2

In the NTP two-generation reproduction study a NOAEL of 0.1% (1 mg/mL) was determined, based on the effects observed in the F1 and F2 generation treated with 0.2% oxalic acid.

In assessing the hazard of oxalic acid, it should be kept in mind that oxalic acid is a natural substance which is present in various food substances, and in this way is consumed by the general population daily. From Gold et al (2001), the following table was derived, in which the average daily consumption of oxalic acid containing food is summarized. A total average daily consumption of 68.4 mg oxalic acid can be calculated from this table.

Food substance (average daily consumption)

Average daily oxalic acid consumption

Coffee (500 mL)

25.2 mg

Carrot (boiled, 12.1 g)

22.7 mg

Tea (60.2 mL)

6.67 mg

Chocolate (cocoa solids, 3.34 g)

3.91 mg

Tomato (88.7 g)

3.24 mg

Celery (7.95 g)

1.39 mg

Potato (54.9 g)

1.26 mg

Corn (33.8 g)

1.12 mg

Apple (32.0 g)

704 µg

(10.5 g)

651 µg

Lettuce (14.9 g)

447 µg

Broccoli (6.71 g)

268 µg

Strawberry (4.38 g)

261 µg

Cabbage (boiled, 12.9 g)

155 µg

Grapes (11 g)

138 µg

Cucumber (raw flesh, 11.8 g)

118 µg

Peach (canned, 9.58 g)

115 µg

Onions (green, cooked, 137 mg)

31.5 µg



Short description of key information:
Effects on fertility:
NOAEL 0.1% in drinking water for mice (1 mg/mL)

Effects on developmental toxicity

Description of key information
No key study selected
Additional information

Two studies concerning developmental toxicity/teratogenicity were perfomed. The results are summarized in the following table.

Study reference

Study type

Results

Reliability

NON KEY_2001_lit_Klug

Embryotoxicity: whole embryo culture test (in vitro), two dose levels (1 and 2 mM)

NOEC 1 mM, based on reduction in value for crown-rump length

2

NON KEY_1980_lit_Sheikh-Omar

Exposure of pregnant rats, effects on dams and foetuses, pilot study: 0.03, 0.05 and 0.06 g/animal/d, main study: 0.035 and 0.045 g/animal/d

Observations in the pilot study (changes comparable to tubulonephrosis in newborn exposed to lowest dose level) could not be reproduced in the main study.

2

Although the results of both studies indicate possible developmental toxicity of oxalic acid, the results are discussable and cannot be used for hazard assessment. In the in vitro embryotoxicity test oxalic acid showed severe dysmorphogenesis in 100% of the cultured embryos at 2 mM, combined with significantly lower growth and differentiation variables. Although at 1 mM a significant reduction of crown-rump length was recorded, the authors approximate the NEC to be rather close to 1 mM. However, it should be kept in mind that in the whole embryo culture test, direct exposure of embryos is investigated. To determine actual developmental toxicity, the bioavailabilty of oxalic acid in vivo should be taken into account. The study by Sheikh-Omar et al (1980) provides some information on developmental toxicity of oxalic, however, as the results could not be reproduced, the study cannot be used for hazard assessment.

In assessing the hazard of oxalic acid, it should be kept in mind that oxalic acid is a natural substance which is present in various food substances, and in this way is consumed by the general population daily. From Gold et al (2001), the following table was derived, in which the average daily consumption of oxalic acid containing food is summarized. A total average daily consumption of 68.4 mg oxalic acid can be calculated from this table.

Food substance (average daily consumption)

Average daily oxalic acid consumption

Coffee (500 mL)

25.2 mg

Carrot (boiled, 12.1 g)

22.7 mg

Tea (60.2 mL)

6.67 mg

Chocolate (cocoa solids, 3.34 g)

3.91 mg

Tomato (88.7 g)

3.24 mg

Celery (7.95 g)

1.39 mg

Potato (54.9 g)

1.26 mg

Corn (33.8 g)

1.12 mg

Apple (32.0 g)

704 µg

(10.5 g)

651 µg

Lettuce (14.9 g)

447 µg

Broccoli (6.71 g)

268 µg

Strawberry (4.38 g)

261 µg

Cabbage (boiled, 12.9 g)

155 µg

Grapes (11 g)

138 µg

Cucumber (raw flesh, 11.8 g)

118 µg

Peach (canned, 9.58 g)

115 µg

Onions (green, cooked, 137 mg)

31.5 µg

Toxicity to reproduction: other studies

Additional information

The studies concerning reprotoxicity are summarized in the following table:

Study reference

Study type

Results

Reliability

KEY_1985_EHRT_NTP85-322

2-generation study in mice, dose levels 0, 0.1 and 0.2% in drinking water

F1, 0.2%: reduced nr of litters per pair, reduced litter weights

F2, 0.2%: reduced nr of live pups, reduced nr of live female pups, reduced prostate weight, increased kidney weight, increased incidence abnormal sperm

2

NON KEY_1977_lit_Goldman

Oral toxicity study via food (2,5 and 5%), 70 days, effects on growth and reproduction

Decrease in growth rate, body weight, reproductive tissue weights at both dose levels

2

In the NTP two-generation reproduction study, a NOAEL of 0.1% (1 mg/mL) was observed, based on significant reduction in number of litters per pair and adjusted live pup weights in the F1 generation treated with 0.2% oxalic acid, and reduction in number of live pups, number of live female pups, and prostate weight, as well as increased kidney weight and incidence abnormal sperm in the F2 generation treated with 0.2% oxalic acid. In the oral toxicity study via food, effects on reproductive tissue weight was observed in both 2,5 and 5.0% oxalic acid in food. Based on these studies, the most critical effect was found in the NTP study, resulting in a NOAEL of 0.1% (1 mg/mL) in drinking water.

In assessing the hazard of oxalic acid, it should be kept in mind that oxalic acid is a natural substance which is present in various food substances, and in this way is consumed by the general population daily. From Gold et al (2001), the following table was derived, in which the average daily consumption of oxalic acid containing food is summarized. A total average daily consumption of 68.4 mg oxalic acid can be calculated from this table.

Food substance (average daily consumption)

Average daily oxalic acid consumption

Coffee (500 mL)

25.2 mg

Carrot (boiled, 12.1 g)

22.7 mg

Tea (60.2 mL)

6.67 mg

Chocolate (cocoa solids, 3.34 g)

3.91 mg

Tomato (88.7 g)

3.24 mg

Celery (7.95 g)

1.39 mg

Potato (54.9 g)

1.26 mg

Corn (33.8 g)

1.12 mg

Apple (32.0 g)

704 µg

(10.5 g)

651 µg

Lettuce (14.9 g)

447 µg

Broccoli (6.71 g)

268 µg

Strawberry (4.38 g)

261 µg

Cabbage (boiled, 12.9 g)

155 µg

Grapes (11 g)

138 µg

Cucumber (raw flesh, 11.8 g)

118 µg

Peach (canned, 9.58 g)

115 µg

Onions (green, cooked, 137 mg)

31.5 µg

Justification for classification or non-classification

The information regarding the potssium trihydrogen dioxalate has been provided by read-across from oxalic acid. Based upon the standard classification criteria (Commission Directive 2001/59/EC of August 2001) and the available information, oxalic acid does not have to be classified as toxic to development or reproduction.

Additional information