Potassium tetrahydroborate

Toxicity to reproduction

Administrative data

Endpoint:

three-generation reproductive toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Toxicologic studies on borax and boric acid.

Author:

Weir R. J., Fisher R. S.

Year:

1972

Bibliographic source:

Toxicology and Applied Pharmacology 2, 23/3, p. 351 - 364.

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

No guideline specified, but conforms to the standard 3 generation 2 litters per generation multi-generation studies normally used at that time.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Boric acid

EC Number:

233-139-2

EC Name:

Boric acid

Cas Number:

10043-35-3

Molecular formula:

H3BO3

IUPAC Name:

Boric acid

Test material form:

solid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Source: Charles River Laboratory
Weight at study initiation: (P) 110 - 150 g
Diet: Ad libitum
Housing: Prior to initiation of the first breeding phase, the animals were maintained in individual cages and fed their respective diets for 14 weeks until they reached maturity.

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on exposure:

0, 670, 2000 or 6700 ppm boric acid (0, 117, 350 and 1,170 ppm boron) in the diet, equivalent to 0, 34 (5.9), 100 (17.5) and 336 (58.5) mg boric acid (boron) mg/kg bw/day.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 ppm (nominal)

Doses / concentrations 2

Dose / conc.:

117 ppm (nominal)

Doses / concentrations 3

Dose / conc.:

350 ppm (nominal)

Doses / concentrations 4

Dose / conc.:

1 170 ppm (nominal)

No. of animals per sex per dose:

8 males and 16 females per group

Control animals:

yes, plain diet

Details on study design:

At 24 hr after birth, the litters were reduced to a maximum of 8 progeny to be raised. The first filial generation (F1A) was carried through weaning and discarded. The parental generation (P1) was rebred to produce their second litter (F1B). At the time of weaning, 16 females and 8 males each from the control and test groups were selected at random and designated the second parental generation (P2) for continuation of the reproduction study. These animals were bred to produce the F2A and F2B litters as before. The F2B litter became the P3 generation and were bred to produce the F3A and F3B litters. With the exception ofthe P1, P2 and P3 control and testgroups, necropsies were performed on all rats.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality:

no mortality observed

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

effects observed, treatment-related

Description (incidence and severity):

sterility

Details on results (P0)

Sterility was observed at highest dose.

Effect levels (P0)

1

Key result

Dose descriptor:

LOAEL

Effect level:

336 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

reproductive performance

2

Key result

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Equivalent to 350 ppm boron in the diet. No effect observed

3

Key result

Dose descriptor:

LOAEL

Effect level:

58.5 mg/kg bw/day (nominal)

Based on:

element

Sex:

male/female

Basis for effect level:

reproductive performance

4

Key result

Dose descriptor:

NOAEL

Effect level:

17.5 mg/kg bw/day (nominal)

Based on:

element

Sex:

male/female

Basis for effect level:

other: No effect observed

Results: F1 generation

General toxicity (F1)

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

no mortality observed

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings:

not specified

Other effects:

not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):

not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:

not specified

Effect levels (F1)

1

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

100 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Equivalent to 350 ppm boron in the diet. No effect observed.

2

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

17.5 mg/kg bw/day (nominal)

Based on:

element

Sex:

male/female

Basis for effect level:

other: No effect observed.

Results: F2 generation

General toxicity (F2)

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

no mortality observed

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings:

not specified

Other effects:

not specified

Developmental neurotoxicity (F2)

Behaviour (functional findings):

not specified

Developmental immunotoxicity (F2)

Developmental immunotoxicity:

not specified

Effect levels (F2)

1

Key result

Dose descriptor:

NOAEL

Generation:

F2

Effect level:

100 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Equivalent to 350 ppm boron in the diet. No effect observed.

2

Key result

Dose descriptor:

NOAEL

Generation:

F2

Effect level:

17.5 mg/kg bw/day (nominal)

Based on:

element

Sex:

male/female

Basis for effect level:

other: No effect observed.

Overall reproductive toxicity

1

Key result

Reproductive effects observed:

yes

Lowest effective dose / conc.:

336 mg/kg bw/day (nominal)

Treatment related:

yes

Relation to other toxic effects:

reproductive effects in the absence of other toxic effects

2

Key result

Reproductive effects observed:

yes

Lowest effective dose / conc.:

58.5 other: mg/kg bw/day as boron equivalents

Treatment related:

yes

Relation to other toxic effects:

reproductive effects in the absence of other toxic effects

Any other information on results incl. tables

Table 1: Reproduction data for rats receiving boric acid at 117 and 350 ppm as boron equivalent

Index	Control	117 ppm	350 ppm	Control	117 ppm	350 ppm
	P1 -F1A			P1 -F1B
Fertility index	62.5	87.5	81.3	60.0	87.5	75.0
Lactation index	56.3	96.2	70.3*	58.8	85.6*	80.0*
Live birth index	98.4	96.0	97.2	99.1	99.4	100.0
	P2 -F2A			P2 -F2B
Fertility index	81.3	93.8	93.8	80.0	93.8	93.8
Lactation index	48.3	79.2*	83.1*	92.1	81.0	98.0
Live birth index	97.8	100.0	99.4	98.6	99.4	97.9
	P3 -F3A			P3 -F3B
Fertility index	68.8	100.0	87.5	68.8	93.8	93.8
Lactation index	91.5	82.5	86.5	89.7	86.7	87.9
Live birth index	100.0	99.5	97.9	100.0	99.0	98.8

Fertility index - number of pregnancies/number of rnatings x 100.

Lactation Index = number weaned/number left to nurse x 100.

'Live blrth index - number of pups born alive/number of pups born x 100.

* Significantly higher than control.

Applicant's summary and conclusion

Conclusions:

In rat reproduction studies, doses of 1170 ppm borax or boric acid as boron equivalent were found to interfere with reproduction, while doses of 350 ppm boron in borax and boric acid had no adverse effect on fertility, lactation, littersize, weight or appearance.
At the highest dose of 1100 ppm rats were sterile.
There were no adverse effects on reproduction reported at exposures of 34 and 100 mg/kg bw boric acid (5.9 and 17.5 mg boron equivalents).
Based on these study data, the authors concluded that exposure of rats at levels up to 17.5 mg B/kg bw in the diet in a 3 generation reproduction study was without adverse effect.