myo-inositol-hexakisphosphate 3-phosphohydrolase

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 October 1999 - 14 January 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Version / remarks:

September 1998

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.26 (Sub-Chronic Oral Toxicity Test: Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Version / remarks:

May 1988

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.3100 (90-Day Oral Toxicity in Rodents)

Version / remarks:

June 1996 (Public Draft)

Deviations:

no

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Test material form:

liquid

Details on test material:

Physical appearance: brown liquid
Storage conditions:in a freezer in the dark or, after thawing, in a refrigerator in the dark

Specific details on test material used for the study:

- Aseptic conditions were used since the test substance is very sensitive to microbial growth/contamination.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

500 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

1 500 mg/kg bw/day (nominal)

Doses / concentrations 4

Dose / conc.:

4 500 mg/kg bw/day (nominal)

No. of animals per sex per dose:

10

Control animals:

yes, concurrent no treatment

Results and discussion

Effect levels

1

Key result

Dose descriptor:

NOAEL

Effect level:

4 500 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no adverse effects found based on the absence of any functional disturbance and morphological changes

2

Key result

Dose descriptor:

NOEL

Effect level:

1 500 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

mortality

organ weights and organ / body weight ratios

Target system / organ toxicity

Key result

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

Based on the results of a 90-day oral toxicity study, performed according to OECD guideline 408 and GLP principles, a NOEL of 1500 mg/kg bw/day was established for NPH 54. However, based on the absence of any functional disturbance and morphological changes in the treated animals, a NOAEL of 4500 mg/kg/day was concluded.

Executive summary:

A 90 -day oral toxicity study by daily gavage in the rat was performed with Enxyme preparation from Aspergillus niger (NPH 54). The study was performed according to OECD guideline 408 and GLP principles.

Based on a 14 -day range finding study, previously performed at the test facility, the dose levels for this study were selected to be 0, 500, 1500 and 4500 mg/kg/day. The test substance was administered daily for at least 90 days by oral gavage to SPF-bred Wistar rats. One control group and three treated groups were tested, each consisting of 10 males and 10 females.

The following parameters were evaluated: clinical signs, functional observations, body weight, food consumption and opthalmoscopy. And at termination: clinical pathology, macroscopy, organ weights and microscopy.

Results were as follows: 500 mg/kg bw/day: no treatment related findings; 1500 mg/kg bw/day: no treatment related findings; 4500 mg/kg bw/day: one female died of pyelonephritis which was unrelated to treatment and the spleen:body weight ratio had increased for females. From these results a NOEL of 1500 mg/kg bw/day was established. However, based on the absence of any functional disturbance and morphological changes in the treated animals, a NOAEL of 4500 mg/kg/day was concluded.