Carbamic acid, N-[(1R)-2-hydroxy-1-phenylethyl]-, 1,1-dimethylethyl ester

Long-term toxicity to aquatic invertebrates

Administrative data

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 August 2018 to 10 September 2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Study director have evaluated the deviations from the study plan (Section 12) and the documents have been archived. There were no significant deviations affected the quality or integrity of the study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: GB/T 21828-2008 Chemicals- Daphnia magna reproduction test (Adopted: 1 September 2008).

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

other: European Commission, Directorate General Health and Consumer Protection, Residues: Guidance for generating and reporting methods of analysis in support of pre-registration data requirements for Annex II (part A, Se

Test guideline 3

Qualifier:

equivalent or similar to guideline

Guideline:

other: MEP, P.R. China, the Guidelines for the Testing of Chemicals, Effects on Biotic Systems (the Second Edition), 211 Daphnia magna Reproduction Test". (2013.8).

Test guideline 4

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 211 (Daphnia magna Reproduction Test)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Carbamic acid, N-[(1R)-2-hydroxy-1-phenylethyl]-, 1,1-dimethylethyl ester

EC Number:

600-273-1

Cas Number:

102089-74-7

Molecular formula:

C13H19NO3

IUPAC Name:

Carbamic acid, N-[(1R)-2-hydroxy-1-phenylethyl]-, 1,1-dimethylethyl ester

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Lot number: US17600768
Appearance: White powder containing lumps
Purity: 99.7%
Storage: Room temperature, 15~25°

Sampling and analysis

Analytical monitoring:

yes

Details on sampling:

HPLC Method

Test solutions

Vehicle:

no

Details on test solutions:

Solution of 20 mg/L was prepared before used, a measured weights of 0.0400-0.0403 g of test item was added to 2L water using a stirring rate at 200 ~ 500 rpm 22 ~ 24 hours. The solution was diluted to 1.25, 2.5, 5 and 10 mg/L. 1L solution was prepared. The test was performed with renewal of the test solutions every 48 hours. After test solutions changed, the daphnia was transferred to different chamber with freshly prepared solutions. A concurrent control group was included in parallel.

Test organisms

Test organisms (species):

Daphnia magna

Details on test organisms:

At the start of the test, the animals were less than 24 hours old, and not the first brood progeny. They were derived from a healthy stock (i.e. showing no signs of stress such as high mortality, presence of males and ephippia, delay in the production of the first brood, discolored animals, etc.). The stock animals were maintained in culture conditions (light, temperature, and medium) similar to those to be used in the test.

The condition for the pre-culture was as below:

Temperature: 18-22°C
Light: 16 hours photoperiod daily( I 000-1500 lux for cool white light), 8 hours dark
Feed: concentrated algal suspension
The batch used for this study was: Daphnia magna C20180815

Study design

Test type:

semi-static

Water media type:

freshwater

Total exposure duration:

21 d

Test conditions

Hardness:

above 140 mg/L (as CaCO)

Test temperature:

20±2 °C

pH:

6 ~ 9 (not varying by more than 1.5 units)

Dissolved oxygen:

above 3 mg/L

Nominal and measured concentrations:

Based on the results of the preliminary test, the definitive test was carried out at concentration of 1.25, 2.5, 5, 10 and 20 mg/L (nominal concentration). The actual concentrations of test solutions were measured by HPLC method.

The results showed that for the test solutions of 1.25, 2.5, 5, 10 and 20 mg/L, the arithmetic mean determined concentrations in fresh media were 1.320, 2.345, 4.593,
9. 772 and 18.340 mg/L. The arithmetic mean determined concentrations in old media were 1.286, 2.373, 4.826, 9.444 and 18.959 mg/L.

The overall arithmetic mean determined concentrations were 1.30, 2.36, 4.71, 9.61 and 18.65 mgL, which were 104.3%, 94.3%, 94.2%, 96.1 % and 93.2% of the nominal concentrations.

Details on test conditions:

Based on the preliminary test, the definitive test was conducted with the nominal concentration of 1.25, 2.5, 5, 10 and 20 mg/L, concurrently with a blank control group. For each concentration and control group, 10 animals were used and individually held.

The test was performed with renewal of the test solutions every 48 hours. After test solutions changed, the daphnia was transferred to different chamber with freshly prepared solutions. A concurrent control group was included in parallel.

The offspring produced by each parent animal were removed and counted daily from the appearance of the first brood to prevent them consuming food intended for the parent. Reproductive output per surviving parent animal, i.e. number of living offspring produced during the test per surviving parent, were recorded.The length of the living parent animals (i.e. body length excluding the anal spine) at the end of the test were measured.

Other parameters measured or calculated include: first brood time, total juveniles of each parent.

Reference substance (positive control):

yes

Remarks:

potassium dichromate (K2Cr2O7)

Results and discussion

Effect concentrations

Effect concentrations 1

Key result

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

10 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

reproduction

Effect concentrations 2

Key result

Duration:

21 d

Dose descriptor:

LOEC

Effect conc.:

20 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

reproduction

Results with reference substance (positive control):

Tests with a reference substance of the potassium dichromate (K2Cr2O7) at the test facility are completed quarterly, which are all within the range 0.6 to 2.1 mg/L. The recent EC50,-24 h of the potassium dichromate to Daphnia was 1.34 mg/L, 95% confidences were 1.16-1.53 mg/L (the study number was HI1 85570180)

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Remarks:

The mortality of the parent animals (female Daphnia) was 0 (did not exceed 20%) at the end of the test. The mean number of live offspring produced per parent animal surviving at the end of the test was 200, which was > 60. Hence, the test was valid.

Conclusions:

The 21-day NOEC  and LOEC for all the parameters  were as below:

Item  NOEC LOEC
Total number of juveniles of each parent 10 mg/L 20 mg/L
body length  1.25 mg/L 2.5 mg/L
first brood time 10 mg/L 20 mg/L

Executive summary:

A Daphnia magna Reproduction  test of Boc-phenyl glycinol was conducted with Daphnia magna over 21 days exposure period.

Based  on the  results  of the preliminary  test, the definitive  test was carried  out at concentration of 1.25, 2.5, 5, 10 and 20 mg/L (nominal concentration). The actual concentrations of test solutions were measured by HPLC method.

A concurrent  blank  control  was performed  in  parallel.  10  daphnias  were  used  for the test groups and the control group.  10 daphnias  individually held at test concentrations and control was used.

Based on the results of the preliminary test, a semi-static system renewed at 48 h with solution was used in the definitive test. 

During the 21  days exposure  period,  no  death and visible toxic signs were observed in the control group and test groups.

 

The concentrations of test item were determined  in samples of test media by HPLC method. The overall  arithmetic mean determined concentrations were 1.30,  2.36, 4.71, 9.61 and 18.65 mgL, which were 104.3%, 94.3%, 94.2%, 96.1 % and 93.2% of the nominal concentrations.

Total  number  of juveniles   of each  parent,  body  length,  first  brood  time  were analysis  by a two-sided  Student  T-test  using  a 5%  significance  level  to obtain  the  no observed  effect  concentration  (NOEC)  and the lowest observed  effect concentration (LOEC).

The 21-day NOEC  and LOEC for all the parameters  were as below:

Item	NOEC	LOEC
Total number of juveniles of each parent	10 mg/L	20 mg/L
body length	1.25 mg/L	2.5 mg/L
first brood time	10 mg/L	20 mg/L