Boron orthophosphate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 Oct - 13 Nov 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

The department of health of the government of the United Kingdom

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Boron orthophosphate

EC Number:

236-337-7

EC Name:

Boron orthophosphate

Cas Number:

13308-51-5

Molecular formula:

BPO4

IUPAC Name:

boron(+3) cation phosphate

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: The bodyweight variation did not exceed ± 20% of the initial/mean bodyweight of any previously dosed animal(s).
- Fasting period before study: overnight fast immediately before dosing
- Housing: The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: ad libitum (2014C Teklad Global Rodent diet supplied by Harlan Teklad, Oxon, UK)
- Water: ad libitum; drinking water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): at least 15 per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: distilled water

Details on oral exposure:

For the purpose of the study the test item was freshly prepared, as required, as a suspension in distilled water.
The test item was formulated within two hours of being applied to the test system. It is assumed that the formulation was stable for this duration.
No analysis was conducted to determine the homogeneity, concentration or stability of the test item formulation. This is an exception with regard to GLP and has been reflected in the GLP compliance statement.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made ½, 1, 2, and 4 hours after dosing and subsequently once daily for 14 days. Morbidity and mortality checks were made twice daily. Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes
At the end of the observation period the animals were sacrificed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Preliminary study:

The starting dose in the sighting test was 300 mg/kg bw administered to one female. No mortality was observed, but hunched posture was noted during the day of dosing.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Dose level: 2000 mg/kg bw
Two animals were found dead during the day of dosing or two days after dosing. One animal was sacrificed for humane reasons, due to the occurrence of clinical signs of toxicity that exceeded the severity limit set forth in the UK Home Office Project Licence, four days after dosing (see table 1).

Dose Level: 300 mg/kg bw
There were no deaths.

Clinical signs:

other: Dose level: 2000 mg/kg bw: There were no signs of systemic toxicity noted in the initial treated animal. Hunched posture was noted in 3/4 of the additional treated animals. Signs of systemic toxicity noted in one animal were lethargy, ataxia, pilo-erectio

Gross pathology:

Dose level: 2000 mg/kg bw:
Individual necropsy findings are given in Table 3.
Haemorrhagic, ulcerated and epithelial sloughing of the gastric mucosa were noted at necropsy of the animals that died during the study. Abnormalities noted at necropsy of the animal that was sacrificed due to humane reasons during the study were patchy pallor of the liver and gaseous stomach and small and large intestines. No abnormalities were noted in the surviving animals

Dose Level: 300 mg/kg bw:
Individual necropsy findings are given in Table 6.
No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table 1. Individual clinical observations and mortality data – 2000 mg/kg bw

Dose level mg/kg bw	Animal number and sex	Effects noted after dosing (hours)				Effects noted during periods after doing (days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	2-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	*	0	0	0	0
	3-0 Female	H	H	H	0	0	X
	3-1 Female	H	H	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-2 Female	X°
	3-3 Female	H	HL	H	0	0	0	HPARlEm	HPALRl RdEmDhX*

 

= No signs of systemic toxicity

H = Hunched posture

L = Lethargy

A = Ataxia

P = Pilo-erection

Em = Emaciation

Rl = Laboured respiration

Rd = Decreased respiratory rate

Dh = Dehydration

X = Animal dead

X° = Animal found dead 18 minutes after dosing

X* = Animal sacrificed for humane reasons, due to the occurrence of clinical signs of toxicity that exceeded the severity limit set forth in the UK Home

Office Project Licence 

 

 Table 2. Individual bodyweight and bodyweight changes– 2000 mg/kg bw

Dose level mg/kg	Animal number and sex	Bodyweight (g) at day			Bodyweight (g) at Death	Bodyweight gain (g) during week
		0	7	14		1	2
2000	2-0 Female	169	180	190		11	10
	3-0 Female	157	-	-	149	-	-
	3-1 Female	166	194	207		28	13
	3-2 Female	151	-	-	151	-	-
	3-3 Female	154	-	-	116	-	-

- = animal dead

 

Table 3. Individual Necropsy Findings – 2000 mg/kg bw

Dose level mg/kg	Animal number and sex	Time of death	Macroscopic observations
2000	2-0 Female	Killed day 14	No abnormalities detected
	3-0 Female	Found dead Day 2	Gastric mucosa: haemorrhagic epithelial sloughing
	3-1 Female	Killed day 14	No abnormalities detected
	3-2 Female	Found dead Day 2	Gastric mucosa: haemorrhagic ulcerated
	3-3 Female	Humanely killed Day 4	Liver: patchy pallor Stomach: gaseous Small intestine: gaseous Large intestine: gaseous

 

 

Table 4. Individual clinical observations and mortality data.– 300 mg/kg bw

Dose level mg/kg	Animal number and sex	Effects noted after dosing (hours)				Effects noted during periods after doing (days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
300	1-0 Female	H	H	H	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-3 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

 

0 = No signs of systemic toxicity

H = Hunched posture

 

 

Table 5. Individual bodyweight and bodyweight changes– 300 mg/kg bw

Dose level mg/kg	Animal number and sex	Bodyweight (g) at day			Bodyweight gain (g) during week
		0	7	14	1	2
300	1-0 Female	158	184	200	26	16
	4-0 Female	142	156	182	14	26
	4-1 Female	159	164	188	5	24
	4-2 Female	148	152	174	4	22
	4-3 Female	155	165	182	10	17

 

 

 Table 6. Individual Necropsy Findings– 300 mg/kg bw

Dose level mg/kg	Animal number and sex	Time of death	Macroscopic observations
300	1-0 Female	Killed day 14	No abnormalities detected
	4-0 Female	Killed day 14	No abnormalities detected
	4-1 Female	Killed day 14	No abnormalities detected
	4-2 Female	Killed day 14	No abnormalities detected
	4-3 Female	Killed day 14	No abnormalities detected

 

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

CLP: Cat. 4, H302