Fytic acid

Endpoint summary

Description of key information

Acute Toxicity Oral (published data), rat (Fischer 344/DuCrj) m / f: LD50: 405 mg/kg bw (male); 480 mg/kg bw (female)

Acute Toxicity Oral (published data), mice (ICL-ICR) m / f: LD50: 900 mg/kg bw (male); 1150 mg/kg bw (female)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: Single oral administration

GLP compliance:

no

Remarks:

Study carried out in 1987, before 1 June 2008 (refering to REACH Article 13(4))

Limit test:

no

Specific details on test material used for the study:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Sample was diluted with water. For applied doses (mg/kg bw) please refer to Table 1 in section "Illustration (picture/graph)".

Species:

mouse

Strain:

ICL-ICR

Sex:

male/female

Route of administration:

oral: unspecified

Doses:

- 490 / 740 / 1110 / 1160 / 2500 mg/kg bw (females and males)
- 800 / 960 / 1150 / 1390 / 1670 mg/kg bw (females)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 72 hr
- Frequency of observations and weighing: no weighing
- Other examinations performed: clinical signs

Statistics:

- Litchfield Wilcoxon
- Moving Average

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 150 mg/kg bw

Based on:

test mat.

95% CL:

>= 910 - <= 1 410

Remarks on result:

other: statistics: Litchfield-Wilcoxon

Sex:

female

Dose descriptor:

LD50

Effect level:

1 160 mg/kg bw

Based on:

test mat.

95% CL:

>= 930 - <= 1 440

Remarks on result:

other: Statistics: Moving Average

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

900 mg/kg bw

Based on:

test mat.

95% CL:

>= 540 - <= 1 490

Remarks on result:

other: Statistics: Litchfield-Wilcoxon

Sex:

male

Dose descriptor:

LD50

Effect level:

900 mg/kg bw

Based on:

test mat.

95% CL:

>= 520 - <= 1 560

Remarks on result:

other: Statistics: Moving Average

Mortality:

Most of the deaths in treated male mice occurred within 1 h after administration, whereas those in treated female mice occurred between 1 and 48 h.
For more details please see the attached illustration.

Clinical signs:

other: In the substance-treated animals the following clinical signs were observed: - thinning of the stomach and small intestinal walls - bleeding of the glandular portion of the stomach - hypertrophy of the gallbladder

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 values for acute toxicity (oral) in mice (ICL-ICR) of the test item were reported to be 1150 mg/kg bw (female) and 900 mg/kg bw (male).

Executive summary:

The oral LD50 values of the substance in mice (ICL-ICR) were reported to be 900 (males) and 1150 (females) mg/kg body weight (Litchfield-Wilcoxon statistics).

Most of the deaths in male mice occured within 1h after administration, whereas those in treated female mice occured between 1 and 48h after administration. Thinning of the stomach and small intestinal walls, bleeding of the glandular portion of the stomach, and hypertrophy of the gallbladder were seen in the treated animals.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: single oral administration

GLP compliance:

no

Remarks:

Study carried out in 1987, before 1 June 2008 (refering to REACH Article 13(4))

Limit test:

no

Specific details on test material used for the study:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Sample was diluted with purified water. Volume (ml/kg bw) and dose (g/kg bw): Refer to Table in section "Any other information on materials and methods incl. tables".

Species:

rat

Strain:

Fischer 344/DuCrj

Sex:

male/female

Vehicle:

water

Doses:

0.26 / 0.30 / 0.35 / 0.40 / 0.46 / 0.53 / 0.61 / 0.70 g/kg bw (Volume 0.5 ml/kg bw)

No. of animals per sex per dose:

5

Control animals:

no

Statistics:

Lichtfield-Wilcoxon

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

0.405 other: g/kg bw

Based on:

test mat.

95% CL:

>= 0.311 - <= 0.527

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

0.48 other: g/kg bw

Based on:

test mat.

95% CL:

>= 0.396 - <= 0.581

Mortality:

- Most of deaths occurred ≤24 h after administration
- male: onset after 1h / peak after 3h / last after 63h
- female: onset after 2h / peak after 2.3h / last after 21h

Clinical signs:

other: Marked expansion of the stomach and bleeding of the glandular portion of the stomach were seen.

Table: LD50 of fytic acid in rats

Material	Sex	Death Time (hr.)	Slope Function (Confidence Interval at p = 0.05)	LD50 (g/kg) (Confidence Interval at p = 0.05)
Fytic acid	M	1 (onset) / 3 (peak) / 63 (last)	1.684 (0.098 ~ 2.583)	0.405 (0.311 ~ 0.527)
	F	2 (onset) / 2.3 (peak) / 21 (last)	1.459 (1.112 ~ 1.914)	0.480 (0.396 ~ 0.581)

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 values for acute toxicity (oral) in rats (Fischer 344/DuCrj) of the test item were reported to be 480 mg/kg bw (female) and 405 mg/kg bw (male).

Executive summary:

The oral LD50 values of this test item in rats (Fischer 344/DuCrj) were reported to be 405 (males) and 480 (females) mg/kg body weight.

Most of the deaths in male and female rats occured ≤ 24 h after administration in the treated animals. Marked expansion of the stomach and bleeding of the glandular portion of the stomach were reported in treated animals.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

405 mg/kg bw

Quality of whole database:

The available information comprises two adequate, reliable (Klimisch score 1) and consistent studies (published data). The test procedure of the two studies (published data) are in accordance with generally accepted scientific standards and are described in sufficient detail. Both studies are non-GLP because they were published, before 1 June 2008, in 1987.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

The acute oral toxicity of the test item was investigated in two published scientific studies (from 1987):

Study 1:

A single oral administration to rats (Fischer 344/DuCrj) was followed by a 7-day observation period. Rats were dosed between 260 – 700 mg/kg body weight with in total 8 different doses. Most of the deaths in male and female rats occurred ≤ 24 h after administration in the treated animals. For male rats the onset was after 1 h, the peak of deaths was reached after 3 h and the last death occurred after 63 h. For female rats the onset was also after 2h, the peak of deaths was already reached after 2.3 h and the last death occurred after 21 h. Reported clinical signs of treated animals comprised marked expansion of the stomach and bleeding of the glandular portion of the stomach.

 

Result Study 1: LD50 (rat, oral): 405 mg/kg bw (male); 480 mg/kg bw (female)

 

Study 2:

A single oral administration to mice (ICL-ICR) with 10 different doses between 490 - 2500 mg/kg body weight were conducted. Most of the deaths in male mice occurred within 1h after administration, whereas those in treated female mice occurred between 1 and 48h after administration. Thinning of the stomach and small intestinal walls, bleeding of the glandular portion of the stomach, and hypertrophy of the gallbladder were seen in the treated animals.

 

Results Study 2: LD50 (mice, oral): 900 mg/kg bw (male); 1150 mg/kg bw (female)

 

Overall conclusion for acute oral toxicity:

The two reliable key studies do not contradict each other and are consistent in their results:

- Both studies result in LD50 values lower than the limit of 2000 mg/kg bw (C&L limit) and would result in a classification (Cat.4) of the substance.

- In both studies male animals were more sensitive than female animals.

- In both studies clinical signs after administration were comparable within the expected variability of different test animals (mice vs. rats). In both studies damages to the gastrointestinal tract were reported.

In conclusion, the acute oral toxiticity of the substance is considered to match the worst-case result from the more common rat model system.

 

LD50: 405 mg/kg bw (male); 480 mg/kg bw (female)

 

Acute inhalation toxicity

Not evaluated, because information not required (Regulation (EC) No. 1907/2006, Annex XII).

 

Acute dermal toxicity

Not evaluated, because information not required (Regulation (EC) No. 1907/2006, Annex XII).

Justification for classification or non-classification

According to the CLP Regulation (EC) No.1272/2008 Annex I: 3.1.2.1.: "Substances can be allocated to one of four hazard categories based on acute toxicity by the oral, dermal or inhalation route according to the numeric criteria shown in Table 3.1.1. Acute toxicity values are expressed as (approximate) LD50 (oral, dermal) or LC50 (inhalation) values or as acute toxicity estimates (ATE)."

 

The LD50 values obtained in the acute oral toxicity studies is between > 300 - 2000 mg/kg bw and for this reason the substance is classified in Category 4 (H302) according to the CLP classification criteria.